Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus
Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved pen...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kim, H. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Anmerkung: |
© The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Vegetos - [Singapore] : Springer Singapore, 2005, 36(2022), 1 vom: 30. Sept., Seite 106-118 |
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| Übergeordnetes Werk: |
volume:36 ; year:2022 ; number:1 ; day:30 ; month:09 ; pages:106-118 |
| Links: |
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| DOI / URN: |
10.1007/s42535-022-00492-2 |
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| Katalog-ID: |
SPR04972990X |
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| 520 | |a Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. | ||
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10.1007/s42535-022-00492-2 doi (DE-627)SPR04972990X (SPR)s42535-022-00492-2-e DE-627 ger DE-627 rakwb eng Kim, H. verfasserin aut Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 Fittipaldi, B. aut Hoque, F. aut Wang, C. aut Zefi, O. aut Li, W. aut Goldman, Z. aut Peter, Y. aut Basu, P. (orcid)0000-0002-2053-2739 aut Enthalten in Vegetos [Singapore] : Springer Singapore, 2005 36(2022), 1 vom: 30. Sept., Seite 106-118 (DE-627)670214809 (DE-600)2632294-8 2229-4473 nnns volume:36 year:2022 number:1 day:30 month:09 pages:106-118 https://dx.doi.org/10.1007/s42535-022-00492-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 36 2022 1 30 09 106-118 |
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10.1007/s42535-022-00492-2 doi (DE-627)SPR04972990X (SPR)s42535-022-00492-2-e DE-627 ger DE-627 rakwb eng Kim, H. verfasserin aut Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 Fittipaldi, B. aut Hoque, F. aut Wang, C. aut Zefi, O. aut Li, W. aut Goldman, Z. aut Peter, Y. aut Basu, P. (orcid)0000-0002-2053-2739 aut Enthalten in Vegetos [Singapore] : Springer Singapore, 2005 36(2022), 1 vom: 30. Sept., Seite 106-118 (DE-627)670214809 (DE-600)2632294-8 2229-4473 nnns volume:36 year:2022 number:1 day:30 month:09 pages:106-118 https://dx.doi.org/10.1007/s42535-022-00492-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 36 2022 1 30 09 106-118 |
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10.1007/s42535-022-00492-2 doi (DE-627)SPR04972990X (SPR)s42535-022-00492-2-e DE-627 ger DE-627 rakwb eng Kim, H. verfasserin aut Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 Fittipaldi, B. aut Hoque, F. aut Wang, C. aut Zefi, O. aut Li, W. aut Goldman, Z. aut Peter, Y. aut Basu, P. (orcid)0000-0002-2053-2739 aut Enthalten in Vegetos [Singapore] : Springer Singapore, 2005 36(2022), 1 vom: 30. Sept., Seite 106-118 (DE-627)670214809 (DE-600)2632294-8 2229-4473 nnns volume:36 year:2022 number:1 day:30 month:09 pages:106-118 https://dx.doi.org/10.1007/s42535-022-00492-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 36 2022 1 30 09 106-118 |
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10.1007/s42535-022-00492-2 doi (DE-627)SPR04972990X (SPR)s42535-022-00492-2-e DE-627 ger DE-627 rakwb eng Kim, H. verfasserin aut Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 Fittipaldi, B. aut Hoque, F. aut Wang, C. aut Zefi, O. aut Li, W. aut Goldman, Z. aut Peter, Y. aut Basu, P. (orcid)0000-0002-2053-2739 aut Enthalten in Vegetos [Singapore] : Springer Singapore, 2005 36(2022), 1 vom: 30. Sept., Seite 106-118 (DE-627)670214809 (DE-600)2632294-8 2229-4473 nnns volume:36 year:2022 number:1 day:30 month:09 pages:106-118 https://dx.doi.org/10.1007/s42535-022-00492-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 36 2022 1 30 09 106-118 |
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10.1007/s42535-022-00492-2 doi (DE-627)SPR04972990X (SPR)s42535-022-00492-2-e DE-627 ger DE-627 rakwb eng Kim, H. verfasserin aut Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 Fittipaldi, B. aut Hoque, F. aut Wang, C. aut Zefi, O. aut Li, W. aut Goldman, Z. aut Peter, Y. aut Basu, P. (orcid)0000-0002-2053-2739 aut Enthalten in Vegetos [Singapore] : Springer Singapore, 2005 36(2022), 1 vom: 30. Sept., Seite 106-118 (DE-627)670214809 (DE-600)2632294-8 2229-4473 nnns volume:36 year:2022 number:1 day:30 month:09 pages:106-118 https://dx.doi.org/10.1007/s42535-022-00492-2 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 36 2022 1 30 09 106-118 |
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Enthalten in Vegetos 36(2022), 1 vom: 30. Sept., Seite 106-118 volume:36 year:2022 number:1 day:30 month:09 pages:106-118 |
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Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Antibiotic tolerance</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">-Alanyl-</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">-alanine carboxypeptidases Pbp4</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Group B streptococcus</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mechanisms of tolerance</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fittipaldi, B.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hoque, F.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, C.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zefi, O.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Li, W.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Goldman, Z.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Peter, Y.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Basu, P.</subfield><subfield code="0">(orcid)0000-0002-2053-2739</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Vegetos</subfield><subfield code="d">[Singapore] : Springer Singapore, 2005</subfield><subfield code="g">36(2022), 1 vom: 30. 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|
| author |
Kim, H. |
| spellingShingle |
Kim, H. misc Antibiotic tolerance misc -Alanyl- misc -alanine carboxypeptidases Pbp4 misc Group B streptococcus misc Mechanisms of tolerance Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus |
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Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus Antibiotic tolerance (dpeaa)DE-He213 -Alanyl- (dpeaa)DE-He213 -alanine carboxypeptidases Pbp4 (dpeaa)DE-He213 Group B streptococcus (dpeaa)DE-He213 Mechanisms of tolerance (dpeaa)DE-He213 |
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misc Antibiotic tolerance misc -Alanyl- misc -alanine carboxypeptidases Pbp4 misc Group B streptococcus misc Mechanisms of tolerance |
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misc Antibiotic tolerance misc -Alanyl- misc -alanine carboxypeptidases Pbp4 misc Group B streptococcus misc Mechanisms of tolerance |
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misc Antibiotic tolerance misc -Alanyl- misc -alanine carboxypeptidases Pbp4 misc Group B streptococcus misc Mechanisms of tolerance |
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Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus |
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Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus |
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Kim, H. |
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Kim, H. Fittipaldi, B. Hoque, F. Wang, C. Zefi, O. Li, W. Goldman, Z. Peter, Y. Basu, P. |
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Kim, H. |
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two amino-acid polymorphisms in pbp4 generate penicillin tolerance in group b streptococcus |
| title_auth |
Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus |
| abstract |
Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Abstract Group B streptococci (GBS) bacteria are the leading cause of neonatal infections in the US. GBS strains may exhibit prolonged resilience to clinical treatments, becoming antibiotic tolerant. Penicillin tolerance (PT) in many Gram-positive bacteria is associated with the highly conserved penicillin-binding protein 4 (pbp4). To determine potential amino acid polymorphisms (AAP) associated with PT in GBS, we characterized the pbp4 gene of 48 clinical isolates. Defining PT as a detectable growth of ≥ 1× $ MIC_{90} $ in the penicillin killing and penicillinase regrowth assay, 7/48 (14.6%) of the strains were PT, and 11/48 (22.9%) were characterized as paradoxical-PT (PE–PT). Sequence alignment of pbp4, identified two AAPs, previously found to be in linkage disequilibrium, G168D, and V289I, that were associated with the PT strains. Within the isolates, the mutant pbp4 allele (pbp4mu) was found in 0/30 (0%) of susceptible, as opposed to 5/7 (71.4%) of PT and 7/11 (63.7%) of PE–PT samples ($ χ^{2} $ = 40.1; df = 2; P < 0.001). To confirm the effect of the G168D and V289I substitutions in GBS, we replaced the wild-type pbp4 (pbp4wt) in a susceptible strain (A909) with pbp4mu and substituted the pbp4mu with pbp4wt in a PT strain (090R). Prevalence of pbp4mu in A909 stabilized cell wall peptidoglycan cross-linkage, decreased membrane damage, and penicillin-mediated killing increasing regrowth tolerance. The reverse was seen upon expression of pbp4wt in 090R. Our findings indicate that AAPs in the penicillin-binding protein 4 of GBS generated by two novel single nucleotide polymorphisms (SNPs) in the pbp4 gene are associated with PT and that the occurrence of one or both mutations can serve as biomarkers used in real-time PCR-based screening assays for detection of PT in GBS and consequently improve treatment guidelines. © The Author(s) under exclusive licence to Society for Plant Research 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Two amino-acid polymorphisms in PBP4 generate penicillin tolerance in group B streptococcus |
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Fittipaldi, B. Hoque, F. Wang, C. Zefi, O. Li, W. Goldman, Z. Peter, Y. Basu, P. |
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Fittipaldi, B. Hoque, F. Wang, C. Zefi, O. Li, W. Goldman, Z. Peter, Y. Basu, P. |
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| score |
7.3978004 |