Success of Escherichia coli O25b:H4 ST131 clade C associated with a decrease in virulence

AbstractEscherichia coli of sequence type (ST) 131 resistant to fluoroquinolones and producer of CTX-M-15 is globally one of the major extraintestinal pathogenic E. coli (ExPEC). ST131 phylogenesis showed that multidrug-resistant ST131 strains belong to a clade called C, descending from an ancestral clade called B, comprising mostly antibiotic-susceptible strains. Antibiotic resistance could appear as one of the keys of the clade C global success. We hypothesized that other features of ST131 clade C could contribute to this success since other major global ExPEC clones (ST73, ST95) are mostly antibiotic-susceptible. To test this hypothesis, we measured the growth abilities, early biofilm formation and virulence-factor content of a collection of clade B and clade C strains. Moreover, using competition assays, we measured the capacity of selected representative strains of clades B and C to colonize the mouse intestine and urinary tract, and to kill mice in a septicemia model. Clade B and C strains had similar growth ability. However, clade B strains were more frequently early biofilm producers, expressed mostly faster their type 1 fimbriae and displayed more virulence factor-encoding genes than clade C strains. Clade B outcompeted clade C in the gut and/or urinary tract colonization models and in the septicemia model. These results strongly suggest that clade C strain evolution includes a loss of virulence, i.e. a process that could enhance micro-organism persistence in a given host and thus optimize transmission. This process, associated with acquired antibiotic-resistance, could ensure clade C strain survival in environments under antibiotic pressure.ImportanceExtraintestinal pathogen Escherichia coli (ExPEC) are virulent but mostly antibiotic-susceptible. One worrying exception is ST131, a major multidrug resistant ExPEC clone that has spread worldwide since the 2000s. To contain the emergence of this threatening clone, we need to understand what factors favored its emergence and dissemination. Here, we investigated whether multidrug-resistant ST131 had advantageous phenotypic properties beyond multidrug resistance. To this end, we competed the emergent multidrug-resistant ST131 with its antibiotic-susceptible ancestor in different conditions: biofilm production, in vivo colonization and virulence experiments. In all in vivo competitions, we found that multidrug-resistant ST131 was losing to its ancestor, suggesting a lesser virulence of multidrug-resistant ST131. It was previously described that losing virulence can increase micro-organism persistence in some populations and subsequently its level of transmissibility. Thus, a decreased level of virulence, associated with multidrug resistance, could explain the global success of ST131.

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Success of Escherichia coli O25b:H4 Sequence Type 131 Clade C Associated with a Decrease in Virulence

Infection and Immunity ◽

10.1128/iai.00576-20 ◽

2020 ◽

Vol 88 (12) ◽

Author(s):

Marion Duprilot ◽

Alexandra Baron ◽

François Blanquart ◽

Sara Dion ◽

Cassandra Pouget ◽

...

Keyword(s):

Escherichia Coli ◽

Phylogenetic Analyses ◽

Multidrug Resistant ◽

Sequence Type ◽

Content Type ◽

Gut Colonization ◽

Clade B ◽

Clade C ◽

Severe Infections

ABSTRACT Escherichia coli O25b:H4 sequence type 131 (ST131), which is resistant to fluoroquinolones and which is a producer of CTX-M-15, is globally one of the major extraintestinal pathogenic E. coli (ExPEC) lineages. Phylogenetic analyses showed that multidrug-resistant ST131 strains belong to clade C, which recently emerged from clade B by stepwise evolution. It has been hypothesized that features other than multidrug resistance could contribute to this dissemination since other major global ExPEC lineages (ST73 and ST95) are mostly antibiotic susceptible. To test this hypothesis, we compared early biofilm production, presence of ExPEC virulence factors (VFs), and in vivo virulence in a mouse sepsis model in 19 and 20 epidemiologically relevant strains of clades B and C, respectively. Clade B strains were significantly earlier biofilm producers (P < 0.001), carriers of more VFs (P = 4e−07), and faster killers of mice (P = 2e−10) than clade C strains. Gene inactivation experiments showed that the H30-fimB and ibeART genes were associated with in vivo virulence. Competition assays in sepsis, gut colonization, and urinary tract infection models between the most anciently diverged strain (B1 subclade), one C1 subclade strain, and a B4 subclade recombining strain harboring some clade C-specific genetic events showed that the B1 strain always outcompeted the C1 strain, whereas the B4 strain outcompeted the C1 strain, depending on the mouse niches. All these findings strongly suggest that clade C evolution includes a progressive loss of virulence involving multiple genes, possibly enhancing overall strain fitness by avoiding severe infections, even if it comes at the cost of a lower colonization ability.

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Clonal Structure, Virulence Factor-Encoding Genes and Antibiotic Resistance of Escherichia coli Causing Urinary Tract Infections and Other Extraintestinal Infections in Humans in Spain and France During 2016

10.20944/preprints202002.0463.v1 ◽

2020 ◽

Author(s):

Saskia-Camille Flament-Simon ◽

Marie-Hélène Nicolas-Chanoine ◽

Vanesa García ◽

Marion Duprilot ◽

Noémie Mayer ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Urinary Tract ◽

Virulence Factor ◽

Multidrug Resistant ◽

Clonal Structure ◽

E Coli ◽

Tract Infections ◽

Encoding Genes ◽

Sequence Types

Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent especially in Spain while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of ESBL enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates two isolates belonged to B2-CH14-64-ST1193 i.e the new global emergent MDR clone. To our knowledge, it is the first identification of this emergent clone in Spain. Moreover, a hybrid ExPEC/enteroaggregative isolate belonging to A-CH11-54-ST10 clone was identified.

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Evaluation of Immunocompetent Urinary Tract Infected Balb/C Mouse Model For the Study of Antibiotic Resistance Development Using Escherichia Coli CFT073 Infection

Antibiotics ◽

10.3390/antibiotics8040170 ◽

2019 ◽

Vol 8 (4) ◽

pp. 170 ◽

Cited By ~ 1

Author(s):

Ashok Chockalingam ◽

Sharron Stewart ◽

Lin Xu ◽

Adarsh Gandhi ◽

Murali K. Matta ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Urinary Tract ◽

Bladder Tissue ◽

Resistance Development ◽

Once Daily ◽

E Coli ◽

Low Levels ◽

Tract Infections

Urinary tract infections (UTI) are common worldwide and are becoming increasingly difficult to treat because of the development of antibiotic resistance. Immunocompetent murine models of human UTI have been used to study pathogenesis and treatment but not for investigating resistance development after treatment with antibiotics. In this study, intravesical inoculation of uropathogenic Escherichia coli CFT073 in immunocompetent Balb/c mice was used as a model of human UTI. The value of the model in investigating antibiotic exposure on in vivo emergence of antibiotic resistance was examined. Experimentally infected mice were treated with 20 or 200 mg/kg ampicillin, 5 or 50 mg/kg ciprofloxacin, or 100 or 1000 mg/kg of fosfomycin. Ampicillin and ciprofloxacin were given twice daily at 8 h intervals, and fosfomycin was given once daily. Antibiotic treatment began 24 h after bacterial inoculation and ended after 72 h following the initial treatment. Although minimum inhibitory concentrations (MIC) for the experimental strain of E. coli were exceeded at peak concentrations in tissues and consistently in urine, low levels of bacteria persisted in tissues in all experiments. E. coli from bladder tissue, kidney, and urine grew on plates containing 1× MIC of antibiotic, but none grew at 3× MIC. This model is not suitable for studying emergent resistance but might serve to examine bacterial persistence.

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Antibiotic resistance and virulence genes of extraintestinal pathogenic Escherichia coli from tropical estuary, south India

The Journal of Infection in Developing Countries ◽

10.3855/jidc.5627 ◽

2015 ◽

Vol 9 (05) ◽

pp. 496-504 ◽

Cited By ~ 1

Author(s):

Divya Sukumaran ◽

Abdulla A Mohamed Hatha

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Multidrug Resistance ◽

Virulence Factor ◽

Virulence Genes ◽

Antimicrobial Agents ◽

Diffusion Method ◽

Disk Diffusion Method ◽

E Coli ◽

Virulence Factor Genes

Introduction: Escherichia coli strains can cause a variety of intestinal and extraintestinal diseases. Extraintestinal pathogenic E. coli (ExPEC) strains have the ability to cause severe extraintestinal infections. Multidrug resistance among ExPEC could complicate human infections. Methodology: Escherichia coli strains were isolated during the period of January 2010 to December 2012 from five different stations set at Cochin estuary. Susceptibility testing was determined by the disk-diffusion method using nine different antimicrobial agents. A total of 155 strains of Escherichia coli were screened for the presence of virulence factor genes including papAH, papC, sfa/focDE, iutA,and kpsMT II associated with ExPEC. Results: Among the 155 E. coli isolates, 26 (16.77%), carried two or more virulence genes typical of ExPEC. Furthermore, 19.23% of the ExPEC isolates with multidrug resistance were identified to belong to phylogenetic groups B2 and D. Statistically significant association of iutA gene in ExPEC was found with papC (p < 0.001) and kpsMT II (p < 0.001) genes. ExPEC isolates were mainly resistant to ampicillin (23.07%), tetracycline (19.23%), co-trimoxazole (15.38%), and cefotaxime (15.38%). The adhesion genes papAH and sfa/focDE were positively associated with resistance to gentamicin, chloramphenicol, and cefotaxime (p < 0.05). Conclusions: Co-occurrence of virulence factor genes with antibiotic resistance among ExPEC poses considerable threat to those who use this aquatic system for a living and for recreation.

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Clonal Structure, Virulence Factor-encoding Genes and Antibiotic Resistance of Escherichia coli, Causing Urinary Tract Infections and Other Extraintestinal Infections in Humans in Spain and France during 2016

Antibiotics ◽

10.3390/antibiotics9040161 ◽

2020 ◽

Vol 9 (4) ◽

pp. 161 ◽

Cited By ~ 7

Author(s):

Saskia-Camille Flament-Simon ◽

Marie-Hélène Nicolas-Chanoine ◽

Vanesa García ◽

Marion Duprilot ◽

Noémie Mayer ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Virulence Factor ◽

Multidrug Resistant ◽

Clonal Structure ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Tract Infections ◽

Encoding Genes ◽

Sequence Types

Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent, especially in Spain, while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of extended-spectrum beta-lactamase (ESBL) enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates, two isolates belonged to B2-CH14-64-ST1193, i.e., the new global emergent MDR clone. Moreover, a hybrid extraintestinal pathogenic E.coli (ExPEC)/enteroaggregative isolate belonging to the A-CH11-54-ST10 clone was identified.

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Two levels of specialization in bacteraemicEscherichia colistrains revealed by their comparison with commensal strains

Epidemiology and Infection ◽

10.1017/s0950268816003010 ◽

2016 ◽

Vol 145 (5) ◽

pp. 872-882 ◽

Cited By ~ 15

Author(s):

O. CLERMONT ◽

C. COUFFIGNAL ◽

J. BLANCO ◽

F. MENTRÉ ◽

B. PICARD ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Urinary Tract ◽

Digestive Tract ◽

Virulence Factors ◽

Virulence Factor ◽

Lower Proportion ◽

Gender And Age ◽

Phylogenetic Grouping ◽

Similar Location

SUMMARYBacteraemia caused byEscherichia coliare particularly frequent and severe, contrasting with the commensal character of the strains found in the digestive tract. A better understanding of the relationships between strains of both origins is needed to unravel the pathogenesis of this disease. Two hundred and forty-three commensal strains were compared to 243 bacteraemic strains isolated from adult hosts matched in terms of gender and age, and from similar location and epoch. Phylogenetic grouping, O-type determination, virulence factor content and antibiotic resistance were compared. Compared to commensal strains, the bacteraemic strains were characterized by a higher proportion of B2, C and D phylogroups, and a lower proportion of A, E and F phylogroups. They also had a lower proportion of the B2 subgroup IV (STc141), a higher proportion of virulence factors, and a higher frequency of antibiotic resistance. These differences were more marked for the bacteraemic strains of urinary tract origin with the presence of specific clones, whereas the bacteraemic strains of digestive origin remained non-significantly different from the commensal strains, except for their antibiotic resistance. Thus, two levels of specialization from commensal strains were demonstrated in the bacteraemic strains: resistance to antibiotics in all cases, and virulence for those of urinary tract origin.

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Gene Mutation of Sulfonamide (SulI) and Tetracycline (TetA/B) Is Responsible for Multidrug Resistance (MDR) of Escherichia coli Isolated From Urinary Tract Infections (UTIs) of Egyptian Patients

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz125.008 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S131-S131

Author(s):

Mohamed Abdelmonem ◽

Amira Husseiny Mohamed ◽

Hesham Shafik ◽

Mohamed Shehata ◽

Gamal EL-Sherbiny ◽

...

Keyword(s):

Escherichia Coli ◽

Multidrug Resistance ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Multidrug Resistant ◽

World Health ◽

E Coli ◽

First Choice ◽

Tract Infections ◽

Multiple Drugs

Abstract Escherichia coli (E coli) is one of the most commonly found pathogens in hospitals. Infections such as gastroenteritis, cystitis, urinary tract infections (UTI), meningitis, septicemia, and peritonitis were previously treated with broad-spectrum antibiotics. However, the emergence of infectious diseases involving multidrug-resistant (MDR) bacterial pathogens is still a major threat to human health. This study aimed to investigate the SulI (sulfonamide), TetA (tetracycline), and TetB resistance genes in E coli isolated from urine specimens from hospitalized patients. In the present cross-sectional study, a total of 55 strains of E coli were isolated from urine cultures of patients who had UTIs in ElKasr ElEiny and ELShorta hospitals. Samples were analyzed for bacteriological, biochemical examination, and agar disc-diffusion to evaluate their antibiotic susceptibility patterns. Polymerase chain reaction (PCR) method also was used to detect SulI, TetA/B genes by specific primers. The results suggested that E coli isolates were resistant to all multiple drugs used. Ampicillin showed the highest resistance of all the isolates followed by sulfonamide and tetracycline at 70%, 62%, and 53%, respectively. The lowest resistance detected with levofloxacin was 12%; however, there is no difference in the resistance pattern of gentamycin and aztreonam. The genotypes’ amplification revealed a positive correlation between SulI (sulfonamide) and TetA/B (tetracycline) resistance encoding genes and was shown in all the tested isolates as 100%. In our study, we found a mutation for sulfonamide and tetracycline genes in E coli that was isolated from UTI patients. The mutation is responsible for a multidrug-resistant strain due to the overuse of antibiotics. However, the World Health Organization recommends the use of trimethoprim-sulfamethoxazole and ampicillin as the first choice for UTI treatment. Our study recommends regulating and limiting the use of those antibiotics in order to minimize the dissemination of multidrug resistance for E coli.

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Study of Multidrug Resistance Pattern among Escherichia coli isolated from patients with Urinary tract infection

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9i6.13961 ◽

2016 ◽

Vol 9 (6) ◽

pp. 157

Author(s):

Soniya Goyal ◽

Vikas Beniwal

Keyword(s):

Escherichia Coli ◽

Multidrug Resistance ◽

Urinary Tract ◽

Bacterial Infections ◽

Multidrug Resistant ◽

Resistance Pattern ◽

Male Population ◽

Antimicrobial Drugs ◽

E Coli ◽

Tract Infections

Objective: Urinary tract infections (UTIs) are some of the most common bacterial infections encountered in community and cause of significant morbidity and high medical cost. Escherichia coli is the most common pathogen belongs to Enterobacteriaceae family responsible for majority of UTI infections. Antimicrobial drugs have been routinely prescribed for empirical treatment of UTIs which has led to a dramatic increase in antibiotic resistance pattern of E. coli. The aim of present study was to analyse the multidrug resistance patterns (MDR) of E. coli isolated from UTI patients.Methods: A total of 80 urine samples collected from the patients suspected of having UTI attending Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala were cultured using standard microbiological techniques. Antibiotic susceptibility testing of E.coli was done by using minimum inhibitory concentration (MIC). MIC of tetracycline, doxycycline, azithromycin, erythromycin, ciprofloxacin, levofloxacin, ampicillin, amoxicillin and amikacin was done by agar dilution method.Results: Of the total 46 isolates contributing 33 females and 13 males were confirmed as E. coli. About 51.34% of the female patients belonged to the age group 21-40 yr and 53.84% of the male population belonged to 41-80 yr were found to be more susceptible to UTI infection. All isolates confirmed as E.coli were found to be multidrug resistant. 80% of the isolates exhibited MICs higher than 1000mg/L against β-lactams. 20% of the E. coli isolates exhibited MICs higher than 1000mg/L against ciprofloxacin, amikacin and erythromycin. 23% and 95% of E. coli isolates exhibited MICs less than 128 mg/L against doxycycline and levofloxacin respectively.Conclusion: The present study revealed the decreased susceptibility of the E.coli to all drugs. E. coli resistance profile to beta lactams, quinolones, macrolides, tetracyclines and aminoglycosides were also found to be quite high in this study emphasizing the need to educate public about appropriate use of antibiotics.NA

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Diversity of P1 phage-like elements in multidrug resistant Escherichia coli

Scientific Reports ◽

10.1038/s41598-019-54895-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 12

Author(s):

Carola Venturini ◽

Tiziana Zingali ◽

Ethan R. Wyrsch ◽

Bethany Bowring ◽

Jonathan Iredell ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Multidrug Resistance ◽

Clinical Isolate ◽

Insertion Sequence ◽

Virulence Genes ◽

Multidrug Resistant ◽

Antibiotic Resistant ◽

E Coli ◽

Resistance Markers

AbstractThe spread of multidrug resistance via mobile genetic elements is a major clinical and veterinary concern. Pathogenic Escherichia coli harbour antibiotic resistance and virulence genes mainly on plasmids, but also bacteriophages and hybrid phage-like plasmids. In this study, the genomes of three E. coli phage-like plasmids, pJIE250-3 from a human E. coli clinical isolate, pSvP1 from a porcine ETEC O157 isolate, and pTZ20_1P from a porcine commensal E. coli, were sequenced (PacBio RSII), annotated and compared. All three elements are coliphage P1 variants, each with unique adaptations. pJIE250-3 is a P1-derivative that has lost lytic functions and contains no accessory genes. In pTZ20_1P and pSvP1, a core P1-like genome is associated with insertion sequence-mediated acquisition of plasmid modules encoding multidrug resistance and virulence, respectively. The transfer ability of pTZ20_1P, carrying antibiotic resistance markers, was also tested and, although this element was not able to transfer by conjugation, it was able to lysogenize a commensal E. coli strain with consequent transfer of resistance. The incidence of P1-like plasmids (~7%) in our E. coli collections correlated well with that in public databases. This study highlights the need to investigate the contribution of phage-like plasmids to the successful spread of antibiotic resistant pathotypes.

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Identification of AcrAB-TolC Efflux Pump Genes and Detection of Mutation in Efflux Repressor AcrR from Omeprazole Responsive Multidrug-Resistant Escherichia coli Isolates Causing Urinary Tract Infections

Microbiology Insights ◽

10.1177/1178636119889629 ◽

2019 ◽

Vol 12 ◽

pp. 117863611988962 ◽

Cited By ~ 1

Author(s):

Nandan Chowdhury ◽

Sabrina Suhani ◽

Auditi Purkaystha ◽

Musammat Kulsuma Begum ◽

Topu Raihan ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Urinary Tract ◽

Amino Acid ◽

Antibiotic Susceptibility ◽

Efflux Pump ◽

Multidrug Resistant ◽

Amino Acid Sequences ◽

E Coli ◽

Tract Infections

Antimicrobial resistance poses a threat in the treatment of infectious diseases in Bangladesh as well as in the world. Multidrug-resistant (MDR) Enterobacteriaceae, the most common cause of one such infectious disease, urinary tract infection (UTI), has contributed to the escalating problem of selecting empiric antibiotics against UTIs. The aim of this study was to investigate the presence of the efflux pump in MDR Escherichia coli isolates from UTI in the North-East region of Bangladesh, to isolate and characterize the AcrAB-TolC efflux pump genes of these locally isolated strains and to do mutation analysis of the efflux pump repressor AcrR gene to understand the AcrAB-TolC efflux pump mechanism. In the presence of omeprazole, an efflux pump inhibitor, every MDR E. coli isolate showed increased susceptibility to at least 1 of the 7 antibiotics investigated, indicating that efflux pump might be involved in their antibiotic resistance. Omeprazole decreased the minimum inhibitory concentration of every antibiotics being investigated by 2- to 8-fold. DNA and the deduced amino acid sequences of the polymerase chain reaction (PCR) products analyzed by bioinformatics tools revealed that the chromosomal AcrAB-TolC and AcrR genes were present in all MDR and antibiotic-susceptible E. coli isolates. However, the deduced amino acid sequences of the amplification refractory mutation system (ARMS) PCR product of the AcrR gene revealed that the substitution of arginine to cysteine at position 45 of AcrR was observed only in the MDR E. coli whose antibiotic susceptibility increased in the presence of omeprazole. Data reported herein support the notion that the increased antibiotic susceptibility of the MDR E. coli isolates in the presence of omeprazole might be due to efflux pump(s) inhibition and the AcrAB-TolC efflux pump might be a contributor to antibiotic resistance when the mutation of arginine to cysteine occurs at position 45 of AcrR.

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