scholarly journals Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 714
Author(s):  
Supapit Wongkuna ◽  
Tavan Janvilisri ◽  
Matthew Phanchana ◽  
Phurt Harnvoravongchai ◽  
Amornrat Aroonnual ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Reference Strain ◽  
Toxin Production ◽  
Temporal Variations ◽  
Toxin Gene ◽  
Data Sets ◽  
Clostridioides Difficile ◽  
Life Threatening ◽  
Susceptibility Profiles

Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A−B+CDT− (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT− (8%), five A−B+CDT+ (19%), seven A−B+CDT− (27%), and six A−B−CDT− (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand.

scholarly journals Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Danielle Barrios Steed ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex D. Waldman ◽  
Ahmed Babiker ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Fecal Microbiota Transplantation ◽  
Antibiotic Prescription ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Gram Negative ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Susceptibility Profiles

ABSTRACT Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility. IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.

scholarly journals FliW and CsrA Govern Flagellin (FliC) Synthesis and Play Pleiotropic Roles in Virulence and Physiology of Clostridioides difficile R20291

2021 ◽  
Vol 12 ◽  
Author(s):  
Duolong Zhu ◽  
Shaohui Wang ◽  
Xingmin Sun
Keyword(s):  
Bacterial Colonization ◽  
Toxin Production ◽  
Toxin Gene ◽  
Clostridioides Difficile ◽  
Significant Difference ◽  
Assembly Factor ◽  
Carbon Storage Regulator ◽  
Transcription Suppression ◽  
Post Transcriptional Regulation

Clostridioides difficile flagellin FliC is associated with toxin gene expression, bacterial colonization, and virulence, and is also involved in pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated in C. difficile remains unclear. In Bacillus subtilis, flagellin homeostasis and motility are coregulated by flagellar assembly factor (FliW), flagellin Hag (FliC homolog), and Carbon storage regulator A (CsrA), which is referred to as partner-switching mechanism “FliW-CsrA-Hag.” In this study, we characterized FliW and CsrA functions by deleting or overexpressing fliW, csrA, and fliW-csrA in C. difficile R20291. We showed that fliW deletion, csrA overexpression in R20291, and csrA complementation in R20291ΔWA (fliW-csrA codeletion mutant) dramatically decreased FliC production, but not fliC gene transcription. Suppression of fliC translation by csrA overexpression can be relieved mostly when fliW was coexpressed, and no significant difference in FliC production was detected when only fliW was complemented in R20291ΔWA. Further, loss of fliW led to increased biofilm formation, cell adhesion, toxin production, and pathogenicity in a mouse model of C. difficile infection (CDI), while fliW-csrA codeletion decreased toxin production and mortality in vivo. Our data suggest that CsrA negatively modulates fliC expression and FliW indirectly affects fliC expression through inhibition of CsrA post-transcriptional regulation. In light of “FliW-CsrA-Hag” switch coregulation mechanism reported in B. subtilis, our data also suggest that “FliW-CsrA-fliC/FliC” can regulate many facets of C. difficile R20291 pathogenicity. These findings further aid us in understanding the virulence regulation in C. difficile.

scholarly journals RstA Is a Major Regulator ofClostridioides difficileToxin Production and Motility

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Adrianne N. Edwards ◽  
Brandon R. Anjuwon-Foster ◽  
Shonna M. McBride
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Toxin Production ◽  
Toxin Gene ◽  
Dna Binding Domain ◽  
Content Type ◽  
Toxin Genes ◽  
Clostridioides Difficile ◽  
Species Specific ◽  
Toxin Gene Expression

ABSTRACTClostridioides difficileinfection (CDI) is a toxin-mediated diarrheal disease. Several factors have been identified that influence the production of the two majorC. difficiletoxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified aC. difficileregulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes, andrstAtranscription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds therstApromoter via the predicted DNA-binding domain. Through mutational analysis of therstApromoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genestcdAandtcdB, as well as the promoters for thesigDandtcdRgenes, which encode regulators of toxin gene expression. Complementation analyses with theClostridium perfringensRstA ortholog and a multispecies chimeric RstA protein revealed that theC. difficileC-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production.IMPORTANCEClostridioides difficileis an anaerobic, gastrointestinal pathogen of humans and other mammals.C. difficileproduces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly binds its own promoter DNA to repress its own gene transcription. In addition, our data demonstrate that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. This study provides a novel regulatory link betweenC. difficilesporulation and toxin production. Further, our data suggest thatC. difficiletoxin production is regulated through a direct, species-specific sensing mechanism.

scholarly journals 2435. The Impact of Treatment Strategy and Toxin Status on Outcomes of Patients with Clostridioides difficile Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S842-S842
Author(s):  
Daniel Friedman ◽  
Karen Zurek ◽  
Leyla Asadi ◽  
Mao-Cheng Lee ◽  
Holly Hoang
Keyword(s):  
Treatment Guidelines ◽  
Retrospective Chart Review ◽  
Toxin Production ◽  
Toxin Gene ◽  
Composite Outcome ◽  
Related Complication ◽  
Clostridioides Difficile ◽  
Increased Risk ◽  
Treatment Escalation ◽  
The Impact

Abstract Background Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality and management continues to evolve. For laboratories that diagnose by detection of toxin gene, it is unclear whether reporting toxin production is additive to patient care. Furthermore, is there still a role for metronidazole (MNZ) given treatment guidelines now recommend vancomycin (VAN) as first-line therapy for non-severe cases? We analyzed cases of CDI in our hospital to assess outcomes of patients on MNZ vs. VAN and with or without toxin production. Methods A retrospective chart review of inpatients with CDI (based on detection of C. difficile toxin gene by PCR) was conducted between November 2017 and August 2018. Comparison of demographics and outcomes was performed in a) cases that were toxin-positive by enzyme immunoassay vs. negative and b) non-severe cases initially managed with MNZ vs. VAN. Results 76 patients were included (46 toxin-positive, 30 toxin-negative). Toxin-positive patients were older (mean age 77 vs. 62, p = 0.002) but had similar disease severity and initial treatment. A CDI recurrence occurred in 22% vs 0% in the toxin-positive cases (p = 0.006). Any CDI-related complication occurred in 23% of toxin-negative and 35% of toxin-positive cases (ns). After adjusting for toxin-status, age, and severity, the odds ratio of the composite outcome of any complication with toxin-positive CDI was not significant (OR 1.45 95% CI 0.45 -4.6, p = 0.52). There were 37 (49%) patients with non-severe CDI (27 MNZ, 10 VAN). Patients treated with VAN had higher stooling/day (6.3 vs 4.4, p = 0.04) and heart rate (p = 0.02). Initial MNZ use was associated with treatment escalation in 48% of cases compared with 10% in those treated with VAN alone (p = 0.03). CDI-associated mortality was higher in the VAN group (2/10 vs 0/27, p = 0.017). The rate of other complications was not significantly different. Conclusion Although no difference in the composite outcome of any CDI-related complication was detected between toxin positive vs negative patients, toxin-positivity may predict patients at risk for subsequent recurrence. Patients with non-severe CDI did not have increased risk of complications when managed with MNZ; however, they were more likely to require treatment escalation. Disclosures All authors: No reported disclosures.

scholarly journals RstA is a Major Regulator ofClostridioides difficileToxin Production and Motility

2018 ◽  
Author(s):  
Adrianne N. Edwards ◽  
Brandon R. Anjuwon-Foster ◽  
Shonna M. McBride
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Toxin Production ◽  
Binding Domain ◽  
Toxin Gene ◽  
Dna Binding Domain ◽  
Toxin Genes ◽  
Clostridioides Difficile ◽  
Species Specific ◽  
Toxin Gene Expression

ABSTRACTClostridioides difficileinfection (CDI) is a toxin-mediated disease. Several factors have been identified that influence the production of the two majorC. difficiletoxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified aC. difficileregulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes andrstAtranscription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds therstApromoter via the predicted DNA-binding domain. Through mutational analysis of therstApromoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genes,tcdAandtcdB, as well as the promoters for thesigDandtcdRgenes, which encode regulators of toxin gene expression. Complementation analyses with theClostridium perfringensRstA ortholog and a multi-species chimeric RstA protein revealed that theC. difficileC-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production.IMPORTANCEClostridioides difficileis an anaerobic, gastrointestinal pathogen of humans and other mammals.C. difficileproduces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside of the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. In addition, the ability for RstA to bind DNA and repress toxin production requires the species-specific domain predicted to respond to small quorum-sensing peptides. This study provides a novel regulatory link betweenC. difficilesporulation and toxin production. Further, our data suggest thatC. difficiletoxin production is regulated through a direct sensing mechanism.

scholarly journals Strain-Dependent RstA Regulation of Clostridioides difficile Toxin Production and Sporulation

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Adrianne N. Edwards ◽  
Ellen G. Krall ◽  
Shonna M. McBride
Keyword(s):  
Gene Expression ◽  
Gastrointestinal Tract ◽  
Toxin Production ◽  
Spore Formation ◽  
Toxin Gene ◽  
Disease Symptoms ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Toxin Gene Expression ◽  
Strain Dependent

ABSTRACT The anaerobic spore former Clostridioides difficile causes significant diarrheal disease in humans and other mammals. Infection begins with the ingestion of dormant spores, which subsequently germinate within the host gastrointestinal tract. There, the vegetative cells proliferate and secrete two exotoxins, TcdA and TcdB, which cause disease symptoms. Although spore formation and toxin production are critical for C. difficile pathogenesis, the regulatory links between these two physiological processes are not well understood and are strain dependent. Previously, we identified a conserved C. difficile regulator, RstA, that promotes sporulation initiation through an unknown mechanism and directly and indirectly represses toxin and motility gene transcription in the historical isolate 630Δerm. To test whether perceived strain-dependent differences in toxin production and sporulation are mediated by RstA, we created an rstA mutant in the epidemic ribotype 027 strain R20291. RstA affected sporulation and toxin gene expression similarly but more robustly in R20291 than in 630Δerm. In contrast, no effect on motility gene expression was observed in R20291. Reporter assays measuring transcriptional regulation of tcdR, the sigma factor gene essential for toxin gene expression, identified sequence-dependent effects influencing repression by RstA and CodY, a global nutritional sensor, in four diverse C. difficile strains. Finally, sequence- and strain-dependent differences were evident in RstA negative autoregulation of rstA transcription. Altogether, our data suggest that strain-dependent differences in RstA regulation contribute to the sporulation and toxin phenotypes observed in R20291. Our data establish RstA as an important regulator of C. difficile virulence traits. IMPORTANCE Two critical traits of Clostridioides difficile pathogenesis are toxin production, which causes disease symptoms, and spore formation, which permits survival outside the gastrointestinal tract. The multifunctional regulator RstA promotes sporulation and prevents toxin production in the historical strain 630Δerm. Here, we show that RstA exhibits stronger effects on these phenotypes in an epidemic isolate, R20291, and additional strain-specific effects on toxin and rstA expression are evident. Our data demonstrate that sequence-specific differences within the promoter for the toxin regulator TcdR contribute to the regulation of toxin production by RstA and CodY. These sequence differences account for some of the variability in toxin production among isolates and may allow strains to differentially control toxin production in response to a variety of signals.

scholarly journals FliW and CsrA govern flagellin (FliC) synthesis and play pleiotropic roles in virulence and physiology of Clostridioides difficile R20291

2021 ◽  
Author(s):  
Duolong Zhu ◽  
Shaohui Wang ◽  
Xingmin Sun
Keyword(s):  
Gene Regulation ◽  
Bacterial Colonization ◽  
Toxin Production ◽  
Toxin Gene ◽  
Flic Gene ◽  
Clostridioides Difficile ◽  
Significant Difference ◽  
Assembly Factor ◽  
Carbon Storage Regulator

Clostridioides difficile is a Gram-positive, spore-forming, and toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. In C. difficile, the expression of flagellar genes is coupled to toxin gene regulation and bacterial colonization and virulence. The flagellin FliC is responsible for pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated is unclear. In Bacillus subtilis, flagellin homeostasis and motility are coregulated by flagellar assembly factor FliW, Flagellin Hag (FliC homolog), and CsrA (Carbon storage regulator A), which is referred to as partner-switching mechanism "FliW-CsrA-Hag". In this study, we characterized FliW and CsrA functions by deleting or overexpressing fliW, csrA, and fliW-csrA in C. difficile R20291. We showed that both fliW deletion or csrA overexpression in R20291, and csrA complementation in R20291ΔWA (fliW-csrA codeletion) dramatically decreased FliC production, however, fliC gene transcription was unaffected. While suppression of fliC translation by csrA overexpression was mostly relieved when fliW was coexpressed, and no significant difference in FliC production was detected when only fliW was complemented in R20291ΔWA. Further, loss of fliW led to increased biofilm formation, cell adhesion, toxin production, and pathogenicity in a mouse model of C. difficile infection (CDI), while fliW-csrA codeletion decreased toxin production and mortality in vivo. Taken together, these data suggest that CsrA negatively modulates fliC expression and FliW indirectly affects fliC expression through inhibition of CsrA post-transcriptional regulation, which seems similar to the "FliW-CsrA-Hag" switch in B. subtilis. Our data also suggest that "FliW-CsrA-fliC/FliC" can regulate many facets of C. difficile R20291 pathogenicity.

Prevalence and Antibiotic Susceptibility of Salmonella Isolated from Foods in Korea from 1993 to 2001

2003 ◽  
Vol 66 (7) ◽  
pp. 1154-1157 ◽  
Author(s):  
Y. H. CHUNG ◽  
S. Y. KIM ◽  
Y. H. CHANG
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Agent ◽  
Antimicrobial Susceptibility ◽  
Antibiotic Susceptibility ◽  
Salmonella Enteritidis ◽  
Antimicrobial Agents ◽  
Intermediate Resistance ◽  
Common Serotypes ◽  
Susceptibility Profiles

This study determined the prevalence of Salmonella in foods widely consumed in Korea from 1993 to 2001, along with antimicrobial susceptibility profiles of Salmonella isolates from these foods for 11 antibiotics. Overall, 41 Salmonella isolates, representing 15 serotypes, were obtained from 2.2% (29 of 1,334) of the samples examined, and most of the Salmonella isolates were recovered from broiler carcasses. The most common serotypes were Salmonella Enteritidis (29.3%), Salmonella Virginia (14.6%), and Salmonella Haart (12.2%). All isolates were screened for antibiotic resistance; 14.6% of the isolates were susceptible to all of the antibiotics, 4.9% were resistant to one antimicrobial agent, 14.6% were resistant to two antimicrobial agents, 22.0% were resistant to three antimicrobial agents, 39.0% were resistant to four antimicrobial agents, and 4.9% were resistant to five antimicrobial agents. Most of the isolates showed resistance or intermediate resistance to streptomycin, ampicillin, carbenicillin, and/or tetracycline.

scholarly journals Characterization of Flagellum and Toxin Phase Variation inClostridioides difficileRibotype 012 Isolates

2018 ◽  
Vol 200 (14) ◽  
Author(s):  
Brandon R. Anjuwon-Foster ◽  
Natalia Maldonado-Vazquez ◽  
Rita Tamayo
Keyword(s):  
Diarrheal Disease ◽  
Low Frequency ◽  
Phase Variation ◽  
Toxin Production ◽  
Toxin Gene ◽  
Phase Variable ◽  
Partial Recovery ◽  
Environmental Isolates ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACTClostridioides difficilecauses diarrheal diseases mediated in part by the secreted toxins TcdA and TcdB.C. difficileproduces flagella that also contribute to motility and bacterial adherence to intestinal cells during infection. Flagellum expression and toxin gene expression are linked via the flagellar alternative sigma factor, SigD. Recently, we identified a flagellar switch upstream of the early flagellar biosynthesis operon that mediates phase variation of both flagellum and toxin production inC. difficilestrain R20291. However, we were unable to detect flagellar switch inversion inC. difficilestrain 630, a ribotype 012 strain commonly used in research labs, suggesting that the strain is phase locked. To determine whether a phase-locked flagellar switch is limited to 630 or present more broadly in ribotype 012 strains, we assessed the frequency and phenotypic outcomes of flagellar switch inversion in multipleC. difficileribotype 012 isolates. The laboratory-adapted strain JIR8094, a derivative of strain 630, and six clinical and environmental isolates were all found to be phase-off, nonmotile, and attenuated for toxin production. We isolated low-frequency motile derivatives of JIR8094 with partial recovery of motility and toxin production and found that additional changes in JIR8094 impact these processes. The clinical and environmental isolates varied considerably in the frequency by which flagellar phase-on derivatives arose, and these derivatives showed fully restored motility and toxin production. Taken together, these results demonstrate heterogeneity in flagellar and toxin phase variation amongC. difficileribotype 012 strains and perhaps other ribotypes, which could impact disease progression and diagnosis.IMPORTANCEC. difficileproduces flagella that enhance bacterial motility and secretes toxins that promote diarrheal disease symptoms. Previously, we found that production of flagella and toxins is coregulated via a flippable DNA element termed the flagellar switch, which mediates the phase-variable production of these factors. Here, we evaluate multiple isolates ofC. difficileribotype 012 strains and find them to be primarily flagellar phase off (flg-off state). Some, but not all, of these isolates showed the ability to switch betweenflg-on and -off states. These findings suggest heterogeneity in the ability ofC. difficileribotype 012 strains to phase-vary flagellum and toxin production, which may broadly apply to pathogenicC. difficile.

scholarly journals Genomic characterization of nine Clostridioides difficile strains isolated from Korean patients with Clostridioides difficile infection

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Seung Woo Ahn ◽  
Se Hee Lee ◽  
Uh Jin Kim ◽  
Hee-Chang Jang ◽  
Hak-Jong Choi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
University Hospital ◽  
Comparative Genomic ◽  
Toxin Gene ◽  
Rrna Gene ◽  
Clostridioides Difficile

Abstract Background Clostridioides difficile infection (CDI) is an infectious nosocomial disease caused by Clostridioides difficile, an opportunistic pathogen that occurs in the intestine after extensive antibiotic regimens. Results Nine C. difficile strains (CBA7201–CBA7209) were isolated from nine patients diagnosed with CDI at the national university hospital in Korea, and the whole genomes of these strains were sequenced to identify their genomic characteristics. Comparative genomic analysis was performed using 51 reference strains and the nine isolated herein. Phylogenetic analysis based on 16S rRNA gene sequences confirmed that all 60 C. difficile strains belong to the genus Clostridioides, while core-genome tree indicated that they were divided into five groups, which was consistent with the results of MLST clade analysis. All strains were confirmed to have a clindamycin antibiotic resistance gene, but the other antibiotic resistance genes differ depending on the MLST clade. Interestingly, the six strains belonging to the sequence type 17 among the nine C. difficile strains isolated here exhibited unique genomic characteristics for PaLoc and CdtLoc, the two toxin gene loci identified in this study, and harbored similar antibiotic resistance genes. Conclusion In this study, we identified the specific genomic characteristics of Korean C. difficile strains, which could serve as basic information for CDI prevention and treatment in Korea.

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