Antimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides difficile Collected in 82 Hospitals in Japan between 2014 and 2016

Shewanella spp., which are known to carry chromosomally located bla OXA genes, have mainly been isolated from marine environments; however, they can also cause infections in humans. In this study, we compared the molecular characteristics of clinical isolates of Shewanella spp. with those originating from environmental sources. All 10 clinical isolates were genetically identified as members of the Shewanella algae clade ( S. algae , S. chilikensis , and S. carassii ); however, all but one of the 13 environmental isolates were identified as Shewanella species members outside the S. algae clade.

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“…AP024613.1 ) as the reference. Core genome SNP analysis was performed as previously described ( 18 ).…”

Section: Methodsmentioning

confidence: 99%

Genetic Environment Surrounding bla _OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla _OXA-55-like in a Carbapenem-Resistant Isolate

Ohama

Aoki

Harada

et al. 2021

mSphere

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“…Consistent with this, highly substituted clades of multiple lineages (ST17(018), ST81(369)/ST37(018) and ST183/ST8(002, Figures 5A, 6A,B) predominated in South East Asia, where cephalosporin use is high (60-62). Adaptation to local prescribing conditions through PBP substitution acquisition offers a possible explanation for the temporal and geographic variation in prevalent C. difficile lineages (6, 8, 19, 47, 58, 63). This may extend to competitive exclusion of lesser PBP substituted strains by more highly substituted ones, a scenario requiring greater numbers of PBP substitutions to carry a fitness cost.…”

Section: Discussionmentioning

confidence: 99%

Penicillin Binding Protein Substitutions Co-occur with Fluoroquinolone Resistance in ‘Epidemic’ Lineages of Multi Drug-Resistant Clostridioides difficile

Dingle

Freeman²,

Didelot

et al. 2022

Preprint

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Clostridioides difficile remains a key cause of healthcare-associated infection, with multi-drug-resistant (MDR) lineages causing high mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species resistance is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins, PBPs). Here, we investigated five C. difficile transpeptidases (PBP1-5) for recent substitutions. Previously published genome assemblies (n=7096) were obtained, representing sixteen geographically widespread lineages, including healthcare-associated MDR ST1(027), ST3(001) and ST17(018). Recent amino acid substitutions were found within PBP1 (n=50) and PBP3 (n=48), ranging from 1-10 substitutions per genome. β-lactam MICs were measured for closely related pairs of wild-type and PBP substituted isolates separated by 20-273 SNPs. Recombination-corrected, dated phylogenies were constructed to date substitution acquisition. Key substitutions such as PBP3 V497L and PBP1 T674I/N/V emerged independently across multiple lineages. They were associated with extremely high cephalosporin MICs; 1-4 doubling dilutions wild-type up to ≤1506μg/ml. Substitution patterns varied by lineage and clade, showed geographic structure, and notably occurred post-1990, coincident with the acquisition of gyrA/B substitutions conferring fluoroquinolone resistance. In conclusion, recent PBP1 and PBP3 substitutions are associated with raised cephalosporin MICs in C. difficile. The co-occurrence of resistance to cephalosporins and fluoroquinolones hinders attempts to understand their relative importance in the dissemination of epidemic lineages. Further controlled studies of cephalosporin and fluoroquinolone stewardship are needed to determine their relative effectiveness in outbreak control.

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“…If C. difficile strains with reduced FDX susceptibilities infect the intestine, these strains may be exposed to sub-MICs of FDX. In a phase III, randomized, nationwide study of FDX versus VAN in Japan, C. difficile strains with high FDX MIC values were isolated from patients after FDX treatment [36]. Using only one strain of C. difficile is a limitation of our research.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of fidaxomicin on biofilm formation in Clostridioides difficile

Hamada

Yamaguchi

Ishii

et al. 2020

Journal of Infection and Chemotherapy

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Clostridioides difficile infection results from a disturbance of the normal microbial flora of the colon, allowing proliferation of C. difficile and toxin production by toxigenic strains. Fidaxomicin, a macrocyclic antibiotic that prevents RNA synthesis in C. difficile and inhibits spore formation, toxin production, and cell proliferation, is clinically effective in treating C. difficile infection. As recent studies have suggested that biofilm formation influences C. difficile colonization and infection in the colon, we undertook the present study to determine the effects of fidaxomicin on C. difficile biofilm formation. Sub-minimum inhibitory concentrations (MICs) of fidaxomicin inhibited biofilm formation by C. difficile UK027 and delayed planktonic growth. Sub-MICs of vancomycin did not inhibit biofilm formation or affect planktonic growth. In C. difficile UK027 exposed to sub-MICs of fidaxomicin, mRNA expression of biofilmrelated flagellin gene fliC was slightly increased compared with that of other biofilm-related genes (pilA1, cwp84, luxS, dccA, and spo0A). In conclusion, this study indicates that sub-MICs of fidaxomicin inhibit C. difficile UK027 biofilm formation by influencing cell growth and fliC transcription.

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Antimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides difficile Collected in 82 Hospitals in Japan between 2014 and 2016

Cited by 21 publications

References 41 publications

Genetic Environment Surrounding bla _OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla _OXA-55-like in a Carbapenem-Resistant Isolate

Genetic Environment Surrounding bla _OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla _OXA-55-like in a Carbapenem-Resistant Isolate

Penicillin Binding Protein Substitutions Co-occur with Fluoroquinolone Resistance in ‘Epidemic’ Lineages of Multi Drug-Resistant Clostridioides difficile

Inhibitory effect of fidaxomicin on biofilm formation in Clostridioides difficile

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Antimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides difficile Collected in 82 Hospitals in Japan between 2014 and 2016

Cited by 21 publications

References 41 publications

Genetic Environment Surrounding bla OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla OXA-55-like in a Carbapenem-Resistant Isolate

Genetic Environment Surrounding bla OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla OXA-55-like in a Carbapenem-Resistant Isolate

Penicillin Binding Protein Substitutions Co-occur with Fluoroquinolone Resistance in ‘Epidemic’ Lineages of Multi Drug-Resistant Clostridioides difficile

Inhibitory effect of fidaxomicin on biofilm formation in Clostridioides difficile

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Genetic Environment Surrounding bla _OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla _OXA-55-like in a Carbapenem-Resistant Isolate

Genetic Environment Surrounding bla _OXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of bla _OXA-55-like in a Carbapenem-Resistant Isolate