Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance
A 60-year-old male with recurrent bacteremia associated with necrotizing pancreatitis was followed over 17 months, during which six clinical isolates of Providencia were obtained. The index isolate (R1) was susceptible to aztreonam-avibactam (MIC 4 mg/L), but resistance (MIC >64 mg/L) emerged wit...
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2539193 |
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| author | Ka Lip Chew Yuan Qiao Priscillia Lye Joey Cruz Cabang Nur Aisyah Binte Abu Bakar Ker Xin Tan Jeanette Teo |
| author_facet | Ka Lip Chew Yuan Qiao Priscillia Lye Joey Cruz Cabang Nur Aisyah Binte Abu Bakar Ker Xin Tan Jeanette Teo |
| author_sort | Ka Lip Chew |
| collection | DOAJ |
| description | A 60-year-old male with recurrent bacteremia associated with necrotizing pancreatitis was followed over 17 months, during which six clinical isolates of Providencia were obtained. The index isolate (R1) was susceptible to aztreonam-avibactam (MIC 4 mg/L), but resistance (MIC >64 mg/L) emerged with isolate B1, collected one month later, and persisted in subsequent isolates. To investigate the genomic and phenotypic evolution of six Providencia clinical isolates, focusing on mechanisms underlying the emergence of aztreonam-avibactam resistance. Whole-genome sequencing was performed to determine species identity, phylogenetic relationships, and resistance determinants. Average nucleotide identity (ANI) and in silico DNA–DNA hybridization (DDH) were used to confirm species classification. Comparative genomic analysis with R1 as a reference identified mutations associated with resistance. Structural modelling assessed the functional impact of key mutations. All isolates were sequence type ST44. Phylogenomic analysis revealed the isolates were more closely related to Providencia hangzhouensis than P. rettgeri, supported by ANI (97%) and DDH (76%). All isolates harboured blaNDM-1, correlating with carbapenem resistance. Resistant isolates displayed a glycine insertion at position 420 in PBP3 (p.Gly420dup), which structural modelling indicated disrupted aztreonam-avibactam binding. A Gly151Asp substitution in OmpC was also identified, potentially affecting drug permeability. No mutations were observed in other porins (OmpA, OmpD, or OmpW). This study identifies a glycine insertion in PBP3 as a novel mechanism driving aztreonam-avibactam resistance in Providencia, supported by structural modelling and additional mutations in OmpC. This study provides evidence of a novel resistance mechanism to aztreonam-avibactam in Providencia, driven by a glycine insertion in PBP3 and supported by alterations in OmpC. |
| format | Article |
| id | doaj-art-bdacb74451074833b7a3f88417660370 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-bdacb74451074833b7a3f884176603702025-08-20T03:59:25ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2539193Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistanceKa Lip Chew0Yuan Qiao1Priscillia Lye2Joey Cruz Cabang3Nur Aisyah Binte Abu Bakar4Ker Xin Tan5Jeanette Teo6Department of Laboratory Medicine, National University Hospital, SingaporeNanyang Link, School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University, SingaporeDivision of Infectious Diseases, Department of Medicine, Alexandra Hospital, SingaporeDepartment of Laboratory Medicine, National University Hospital, SingaporeDepartment of Laboratory Medicine, National University Hospital, SingaporeDepartment of Laboratory Medicine, National University Hospital, SingaporeDepartment of Laboratory Medicine, National University Hospital, SingaporeA 60-year-old male with recurrent bacteremia associated with necrotizing pancreatitis was followed over 17 months, during which six clinical isolates of Providencia were obtained. The index isolate (R1) was susceptible to aztreonam-avibactam (MIC 4 mg/L), but resistance (MIC >64 mg/L) emerged with isolate B1, collected one month later, and persisted in subsequent isolates. To investigate the genomic and phenotypic evolution of six Providencia clinical isolates, focusing on mechanisms underlying the emergence of aztreonam-avibactam resistance. Whole-genome sequencing was performed to determine species identity, phylogenetic relationships, and resistance determinants. Average nucleotide identity (ANI) and in silico DNA–DNA hybridization (DDH) were used to confirm species classification. Comparative genomic analysis with R1 as a reference identified mutations associated with resistance. Structural modelling assessed the functional impact of key mutations. All isolates were sequence type ST44. Phylogenomic analysis revealed the isolates were more closely related to Providencia hangzhouensis than P. rettgeri, supported by ANI (97%) and DDH (76%). All isolates harboured blaNDM-1, correlating with carbapenem resistance. Resistant isolates displayed a glycine insertion at position 420 in PBP3 (p.Gly420dup), which structural modelling indicated disrupted aztreonam-avibactam binding. A Gly151Asp substitution in OmpC was also identified, potentially affecting drug permeability. No mutations were observed in other porins (OmpA, OmpD, or OmpW). This study identifies a glycine insertion in PBP3 as a novel mechanism driving aztreonam-avibactam resistance in Providencia, supported by structural modelling and additional mutations in OmpC. This study provides evidence of a novel resistance mechanism to aztreonam-avibactam in Providencia, driven by a glycine insertion in PBP3 and supported by alterations in OmpC.https://www.tandfonline.com/doi/10.1080/22221751.2025.2539193Porinpenicillin-binding protein 3carbapenem-resistant enterobacterales (CRE)whole-genome sequencingaztreonam-avibactam |
| spellingShingle | Ka Lip Chew Yuan Qiao Priscillia Lye Joey Cruz Cabang Nur Aisyah Binte Abu Bakar Ker Xin Tan Jeanette Teo Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance Emerging Microbes and Infections Porin penicillin-binding protein 3 carbapenem-resistant enterobacterales (CRE) whole-genome sequencing aztreonam-avibactam |
| title | Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance |
| title_full | Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance |
| title_fullStr | Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance |
| title_full_unstemmed | Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance |
| title_short | Whole-genome analysis of NDM-producing Providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam-avibactam resistance |
| title_sort | whole genome analysis of ndm producing providencia hangzhouensis associated with recurrent bacteraemia with rapid development of aztreonam avibactam resistance |
| topic | Porin penicillin-binding protein 3 carbapenem-resistant enterobacterales (CRE) whole-genome sequencing aztreonam-avibactam |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2539193 |
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