Hypervirulent clade 2, ribotype 019/sequence type 67 Clostridioides difficile strain from Japan

Saito, Ryoichi; Usui, Yukino; Ayibieke, Alafate; Nakajima, Jun; Prah, Isaac; Sonobe, Kazunari; Aiso, Yoshibumi; Ito, Shiori; Itsui, Yasuhiro; Hadano, Yoshiro; Nukui, Yoko; Koike, Ryuji; Tohda, Shuji

doi:10.1186/s13099-019-0336-3

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…For example, while most isolates of ST13 (60%), ST42 (80%) and ST2 (66.7%) were non-producers, most (75%) isolates of ST6 were moderate producers and most of ST104 (57.1%) isolates were strong producers. One isolate which belong to ST43 (mean OD 570 = 2.22) produced a biofilm as strong as the control 630 strain which belong to ST54 ( Saito et al, 2019 ). Two other isolates that belong to ST8 and ST239 had a stronger biofilm production capacity, compared to the control strain (mean OD 570 = 3.93 and 3.34, respectively).…”

Section: Resultsmentioning

confidence: 97%

Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

Rahmoun

Azrad

Peretz

2021

Front. Cell. Infect. Microbiol.

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BackgroundClostridioides difficile (C. difficile) is one of the primary pathogens responsible for infectious diarrhea. Antibiotic treatment failure, occurring in about 30% of patients, and elevated rates of antibiotic resistance pose a major challenge for therapy. Reinfection often occurs by isolates that produce biofilm, a protective barrier impermeable to antibiotics. We explored the association between antibiotic resistance (in planktonic form) and biofilm-production in 123 C. difficile clinical isolates.ResultsOverall, 66 (53.6%) out of 123 isolates produced a biofilm, with most of them being either a strong (44%) or moderate (34.8%) biofilm producers. When compared to susceptible isolates, a statistically higher percentage of isolates with reduced susceptibility to metronidazole or vancomycin were biofilm producers (p < 0.0001, for both antibiotics). Biofilm production intensity was higher among tolerant isolates; 53.1% of the metronidazole-susceptible isolates were not able to produce biofilms, and only 12.5% were strong biofilm-producers. In contrast, 63% of the isolates with reduced susceptibility had a strong biofilm-production capability, while 22.2% were non-producers. Among the vancomycin-susceptible isolates, 51% were unable to produce biofilms, while all the isolates with reduced vancomycin susceptibility were biofilm-producers. Additionally, strong biofilm production capacity was more common among the isolates with reduced vancomycin susceptibility, compared to susceptible isolates (72.7% vs. 18.8%, respectively). The distribution of biofilm capacity groups was statistically different between different Sequence-types (ST) strains (p =0.001). For example, while most of ST2 (66.7%), ST13 (60%), ST42 (80%) isolates were non-producers, most (75%) ST6 isolates were moderate producers and most of ST104 (57.1%) were strong producers.ConclusionsOur results suggest an association between reduced antibiotic susceptibility and biofilm production capacity. This finding reinforces the importance of antibiotic susceptibility testing, mainly in recurrence infections that may be induced by a strain that is both antibiotic tolerant and biofilm producer. Better adjustment of treatment in such cases may reduce recurrences rates and complications. The link of biofilm production and ST should be further validated; if ST can indicate on isolate virulence, then in the future, when strain typing methods will be more available to laboratories, ST determination may aid in indecision between supportive vs. aggressive treatment.

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Section: Resultsmentioning

confidence: 97%

Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

Rahmoun

Azrad

Peretz

2021

Front. Cell. Infect. Microbiol.

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“…Despite having a variant TcdB, 5757-ST67 produced an elevated inflammatory response and alteration of biochemical markers that could be explained by toxin overproduction [ 32 ]. Moreover, mutations in treR (trehalose repressor), CpG depleted genomes [ 31 ] and a PaLoc rather similar to that of strain R202091-ST01 [ 33 ] have been described in this ST, all of which are characteristics of hypervirulent C. difficile strains.…”

Section: Discussionmentioning

confidence: 99%

In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2

et al. 2020

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Background Based on MLST analyses the global population of C. difficile is distributed in eight clades, of which Clade 2 includes the “hypervirulent” NAP1/RT027/ST01 strain along with various unexplored sequence types (STs). Methods To clarify whether this clinically relevant phenotype is a widespread feature of C. difficile Clade 2, we used the murine ileal loop model to compare the in vivo pro-inflammatory (TNF-α, IL-1β, IL-6) and oxidative stress activities (MPO) of five Clade 2 clinical C. difficile isolates from sequence types (STs) 01, 41, 67, and 252. Besides, we infected Golden Syrian hamsters with spores from these strains to determine their lethality, and obtain a histological evaluation of tissue damage, WBC counts, and serum injury biomarkers (LDH, ALT, AST, albumin, BUN, creatinine, Na+, and Cl−). Genomic distances were calculated using Mash and FastANI to explore whether the responses were dictated by phylogeny. Results The ST01 isolate tested ranked first in all assays, as it induced the highest overall levels of pro-inflammatory cytokines, MPO activity, epithelial damage, biochemical markers, and mortality measured in both animal models. Statistically indistinguishable or rather similar outputs were obtained for a ST67 isolate in tests such as tissue damage, neutrophils count, and lethal activity. The results recorded for the two ST41 isolates tested were of intermediate magnitude and the ST252 isolate displayed the lowest pathogenic potential in all animal experiments. This ordering matched the genomic distance of the ST01 isolate to the non-ST01 isolates. Conclusions Despite their close phylogenic relatedness, our results demonstrate differences in pathogenicity and virulence levels in Clade 2 C. difficile strains, confirm the high severity of infections caused by the NAP1/RT027/ST01 strain, and highlight the importance of C. difficile typing.

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“…Clostridium difficile infection or known as CDI has been recognized as a typical HAIs and contributes to a significant proportion of morbidity and mortality among hospitalized patients with case-fatality rates of multiple infections varying from mild diarrhea to pseudomembranous colitis (PMC), especially in the elderly patients on antibiotic treatment. [1][2][3][4][5] In addition, the high health costs associated with CDI increase the government's financial burden on health spending. It was noted that half a million infections were associated with CDI in the United States in 2011 with an incidence rate of 8.75 cases/1,000 adult admissions in 2009.…”

Section: Introductionmentioning

confidence: 99%

“…It was noted that half a million infections were associated with CDI in the United States in 2011 with an incidence rate of 8.75 cases/1,000 adult admissions in 2009. 1 In study of Saito et al, 2019 reported the results of C. difficile ribotyping without information on the prevalence or incidence of CDI in Japan. 2 The incidence of CDI increased from 1.7/1,000 to 2.7/1,000 adults in Korea and 17.1/10,000 hospitalized patients in Shanghai were associated with CDI.…”

Section: Introductionmentioning

confidence: 99%

Clostridium difficile virulence factors as the cause of antibiotic-associated diarrhea (AAD): a literature review

2022

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Clostridium difficile is an anaerobic gram-positive bacillus, capable of forming spores and toxins, transmitted to humans by the faecal-oral route C. difficile infection (CDI) is recognized as a typical cause of healthcare-associated infections (HAIs) and contributes to a significant proportion of morbidity and mortality of hospitalized patients. C. difficile culture and toxin examinations are still minimal in many hospitals in various Asian countries. As a result, reports of C. difficile in Asia are still rare, while reports of cases of CDI in Indonesia are still rare. Several risk factors including advanced age, antibiotic exposure, and hospitalization are strongly associated with CDI. C. difficile has the ability to colonize the large intestine, then release exotoxin proteins (TcdA, TcdB) causing colitis in people with risk factors. A diagnosis of suspected C. difficile infection in a patient with diarrhea without a clear alternative explanation, with relevant risk factors (including long antibiotic consumption, hospitalization events, and elderly age), was then performed microbiological examination to carry out proper management and control of infection. This study aims to review C. difficile virulence factors as the cause of antibiotic-associated diarrhea.

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Hypervirulent clade 2, ribotype 019/sequence type 67 Clostridioides difficile strain from Japan

Cited by 9 publications

References 43 publications

Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile

In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2

Clostridium difficile virulence factors as the cause of antibiotic-associated diarrhea (AAD): a literature review

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