Escherichia coli sequence type 410 with carbapenemases: a paradigm shift within E. coli toward multidrug resistance.

Escherichia coli sequence type ST410 is an emerging carbapenemase-producing multidrug-resistant (MDR) high-risk One-Health clone with the potential to significantly increase carbapenem resistance among E. coli. ST410 belongs to two clades (ST410-A and ST410-B) and three subclades (ST410-B1, ST410-B2, and ST410-B3). After a fimH switch between clades ST410-A and ST410-B1, ST410-B2 and ST410-B3 subclades showed a stepwise progression toward developing MDR. (i) ST410-B2 initially acquired fluoroquinolone resistance (via homologous recombination) in the 1980s. (ii) ST410-B2 then obtained CMY-2, CTX-M-15, and OXA-181 genes on different plasmid platforms during the 1990s. (iii) This was followed by the chromosomal integration of blaCMY-2, fstl YRIN insertion, and ompC/ompF mutations during the 2000s to create the ST410-B3 subclade. (iv) An IncF plasmid "replacement" scenario happened when ST410-B2 transformed into ST410-B3: F36:31:A4:B1 plasmids were replaced by F1:A1:B49 plasmids (both containing blaCTX-M-15) followed by blaNDM-5 incorporation during the 2010s. User-friendly cost-effective methods for the rapid identification of ST410 isolates and clades are needed because limited data are available about the frequencies and global distribution of ST410 clades. Basic mechanistic, evolutionary, surveillance, and clinical studies are urgently required to investigate the success of ST410 (including the ability to acquire successive MDR determinants). Such information will aid with management and prevention strategies to curb the spread of carbapenem-resistant E. coli. The medical community can ill afford to ignore the spread of a global E. coli clone with the potential to end the carbapenem era.

CRISPR-Cas9-mediated IncF plasmid curing in extraintestinal pathogenic Escherichia coli.

IMPORTANCE: Understanding the role of IncF plasmids in the success of drug-resistant bacteria has far-reaching implications for tackling antibiotic resistance. The study's use of a novel CRISPR-Cas9-mediated plasmid-curing system provides a precision tool for dissecting the specific impact of IncF plasmids on ExPEC clones, especially high-risk, multidrug-resistant strains like ST131, ST1193, and ST410. The study offers a crucial stepping stone for future research into understanding how these plasmids influence more complex aspects of bacterial behavior, such as cell invasion and in vivo fitness.

The contributions of multidrug resistant clones to the success of pandemic extra-intestinal Pathogenic Escherichia coli.

INTRODUCTION: High-risk multidrug (MDR) clones have played essential roles in the global emergence and spread of antimicrobial resistance (AMR), especially among Extra-intestinal Escherichia coli (ExPEC). AREAS COVERED: Successful global ExPEC MDR clones are linked with the acquisition of fluoroquinolone resistance, CTX-M enzymes, and with carbapenemases. This article described the underlying mechanisms of fluoroquinolone resistance, the acquisition of CTX-M and carbapenemase genes among three global ExPEC high-risk MDR clones, namely i) ST1193 as being an example of a fluoroquinolone resistant clone. ii) ST131 as an example of a fluoroquinolone resistant and CTX-M clone. iii) ST410 as an example of a fluoroquinolone resistant, CTX-M and carbapenemase clone. This article also highlighted the contributions of these MDR determinants in the evolution of these high-risk MDR clones. EXPERT OPINION: There is an enormous public health burden due to E. coli MDR high-risk clones such as ST1193, ST131 and ST410. These clones have played pivotal roles in the global spread of AMR. Sparse information is available on which specific features of these high-risk MDR clones have enabled them to become such successful global pathogens in relative short time periods.

Acquisition of genomic elements were pivotal for the success of Escherichia coli ST410.

BACKGROUND: Escherichia coli ST410 is an emerging MDR clone linked to blaCTX-M-15 and blaOXA-181. Limited comprehensive data about the global distribution of ST410 clades and mobile genetic elements associated with different ß-lactamases are available. METHODS: Short- and long-read WGS were performed on a collection of ST410 producing carbapenemases (n = 45) obtained from 11 countries. The evolutionary history of global E. coli ST410 was also investigated. RESULTS: OXA-181 and NDM-5 were the most frequent carbapenemases and used different underlying strategies to ensure their successful association with ST410 clades. Our phylogenetic analysis of publicly available ST410 genomes amended the previously published ST410 B subclades: ST410-B1 is identical to B1/H24, ST410-B2 includes B2/H24R and B3/H24Rx, while ST410-B3 corresponds to B4/H24RxC. Long-read WGS identified the following genomic events that likely shaped the evolution of ST410-B3: (i) gyrA and parC mutations were acquired via homologous recombination events; (ii) chromosomal integration of blaCMY-2 among ST410-B3; (iii) the emergence of ST410-B3 from ST410-B2 was accompanied by the replacement of IncFII plasmids harbouring blaCTX-M-15 (i.e. F36:31:A4:B1 in ST410-B2 with F1:A1:B49 plasmids in ST410-B3); and (iv) the NDM-5 gene was integrated within F1:A1:B49 plasmids over time. CONCLUSIONS: The global ST410 population producing carbapenemases is dominated by the ST410-B2 and B3 subclades with varied geographical distribution that requires ongoing genomic surveillance. We provided an updated timeline of pivotal genomic events that have shaped the success of the ST410-B3 subclade.

Escherichia coli ST1193: Following in the Footsteps of E. coli ST131.

Escherichia coli ST1193 is an emerging global multidrug (MDR) high-risk clone and an important cause of community-onset urinary and bloodstream infections. ST1193 is imitating E. coli ST131, the most successful MDR clone of all time. Both clones emerged in the early 1990s by acquiring quinolone resistance-determining region (QRDR) mutations, IncF plasmids, virulence factors, and type 1 pilus (fimH) recombination. They are the only MDR clones that are dominant among unselected E. coli populations. ST131 is the most frequent clone and ST1193 the second most frequent clone among fluoroquinolone/cephalosporin-resistant E. coli isolates. Both clones have played pivotal roles in the global spread of MDR E. coli. ST1193 originated from ST clonal complex 14 (STc14), is lactose nonfermenting, belongs to phylogenetic group B2, and contains the O type O75. Global ST1193 prevalence has been increasing since 2012, even replacing ST131 in certain regions. blaCTX-M genes are rapidly expanding among ST1193 isolates, a scenario that occurred with ST131 during the 2000s. A validated PCR will enable global surveys to determine the extent of ST1193 among One Health E. coli isolates. The rapid emergence of ST1193 is concerning and is adding to the public health burden of MDR E. coli clones. Basic mechanistic, evolutionary, surveillance, and clinical studies are urgently required to investigate the success of ST1193. Such information will aid with management and prevention strategies. The medical community can ill afford to ignore the spread of another global successful MDR high-risk E. coli clone, especially one that is following in the footsteps of E. coli ST131.

Genomic Epidemiology of Global Carbapenemase-Producing Escherichia coli, 2015-2017.

We describe the global molecular epidemiology of 229 carbapenemase-producing Escherichia coli in 36 countries during 2015-2017. Common carbapenemases were oxacillinase (OXA) 181 (23%), New Delhi metallo-ß-lactamase (NDM) 5 (20%), OXA-48 (17%), Klebsiella pneumoniae carbapenemase 2 (15%), and NDM-1 (10%). We identified 5 dominant sequence types (STs); 4 were global (ST410, ST131, ST167, and ST405), and 1 (ST1284) was limited to Turkey. OXA-181 was frequent in Jordan (because of the ST410-B4/H24RxC subclade) and Turkey (because of ST1284). We found nearly identical IncX3-blaOXA-181 plasmids among 11 STs from 12 countries. NDM-5 was frequent in Egypt, Thailand (linked with ST410-B4/H24RxC and ST167-B subclades), and Vietnam (because of ST448). OXA-48 was common in Turkey (linked with ST11260). Global K. pneumoniae carbapenemases were linked with ST131 C1/H30 subclade and NDM-1 with various STs. The global carbapenemase E. coli population is dominated by diverse STs with different characteristics and varied geographic distributions, requiring ongoing genomic surveillance.

Population-based epidemiology of Escherichia coli ST1193 causing blood stream infections in a centralized Canadian region.

Escherichia coli ST1193 is an emerging global clone associated with fluoroquinolone resistance. A population-based study described genomics, clinical factors, susceptibility patterns, and incidence rates of ST1193 (n = 69) causing incident blood stream infections in a centralized Canadian region 2016-18. ST1193 was responsible for community-acquired upper urinary tract infections among the elderly. The incidence rate (IR) per 100,000 person-years among Calgary residents increased from 1.0 (95%confidence interval [95%CI] 0.7-1.5) in 2016, to 1.7 (95%CI 1.3-2.3) in 2018 (p = 0.05). This was mainly due to the significant increase of ST1193 blood stream infections among female long-term care (LTC) residents. ST1193 IR with blaCTX-Ms was 3.18 times higher in 2018 than in 2016 (CI 95% 0.98-13.49). We identified a ST1193 isolate with only a parC S80I mutation that is different from previously published data. The population-based study identified a significant increase over a 2-year period of E. coli ST1193 blood stream infections among elderly females residing in LTC centers. There was also a notable increase of ST1193 with bla CTX-Ms in 2018. The rapid emergence of ST1193 is concerning and adding to the public health burden of multidrug resistant E. coli blood stream infections in Calgary.

The importance of Escherichia coli clonal complex 10 and ST131 among Tanzanian patients on antimicrobial resistance surveillance programs.

The objective of this study was to characterize antimicrobial resistance (AMR) of WHO priority 1 critical pathogen (extrapathogenic Escherichia coli (ExPEC), sequence types (STs), and ST131 clades from patients in Tanzania so as to guide specific antimicrobial therapies and preventive measures. A total of 143 ExPEC strains (128 from pregnant women with urinary tract infections and 15 from children with blood stream infections) were collected between March 2016 and October 2017. These were characterized into ST-fimH clones by a 7-single nucleotide polymorphism quantitative polymerase chain reaction (7-SNP qPCR) and gene sequencing, and to ST131 clades by multiplex PCR. The extended-spectrum beta-lactamases (ESBL) production was 16.1% (23/143), and was predominantly due to the blaCTX-M-15 (91.3%, n=21). ESBL production was significantly more among strains from children (53.3%) than pregnant women (11.7%) (OR (95%CI): 8.61 (2.73-27.15); p-value <0.001)). Approximately 61.5% (n=88) ExPEC were typed into their respective STs/CCs (87 by the 7-SNP qPCR and by an additional of one or two genes sequencing). The commonest STs/CCs among typeable strains were CC10 (28.4%, n=25), ST131 (18.2%, n=16), and ST38 (10.2%, n=9). The ST131 clades (C1 (4, 25.0%) and C2 (6, 37.5%)) were predominantly associated with fluoroquinolone resistance and ESBL production, respectively. Approximately 60.8% of ExPEC strains and all dominant clones were typed by the 7-SNP qPCR by additional sequencing. The multiplex clade PCR allowed linkage of the global clone ST131 with AMR phenotypes. These feasible and user-friendly molecular tools can be routinely used for surveillance programs in resource-limited settings.

The Lyme disease spirochete can hijack the host immune system for extravasation from the microvasculature.

Lyme disease is the most common tick-transmitted disease in the northern hemisphere and is caused by the spirochete Borrelia burgdorferi and related Borrelia species. The constellation of symptoms attributable to this malady results from vascular dissemination of B. burgdorferi throughout the body to invade various tissue types. However, little is known about the mechanism by which the spirochetes can breach the blood vessel wall to reach distant tissues. We have studied this process by direct observation of spirochetes in the microvasculature of living mice using multi-laser spinning-disk intravital microscopy. Our results show that in our experimental system, instead of phagocytizing B. burgdorferi, host neutrophils are involved in the production of specific cytokines that activate the endothelium and potentiate B. burgdorferi escape into the surrounding tissue. Spirochete escape is not induced by paracellular permeability and appears to occur via a transcellular pathway. Neutrophil repurposing to promote bacterial extravasation represents a new and innovative pathogenic strategy.

Spatial distribution of Escherichia coli ST131 C subclades in a centralized Canadian urban region.

INTRODUCTION: Escherichia coli ST131 is the most common multidrug-resistant (MDR) E. coli clone causing bloodstream infections (BSIs) in Calgary. This study describes patient characteristics and spatial distribution of ST131 subclades C1 and C2 causing BSIs in Calgary. METHODS: E. coli from blood (n = 685) obtained in Calgary, Canada, (2016) were PCR screened for ST131 and positives (n = 141) underwent whole genome sequencing. Patient characteristics were analysed using Fisher's Exact/t-tests and spatial analysis was used to identify clusters. RESULTS: Overall, 21% of E. coli was identified as ST131 and clade C dominated the population. ST131-C2 was associated with blaCTX-M-15 and significantly more MDR than ST131-C1. The spatial distribution in Calgary showed that ST131-C1 was mainly present in long-term care (LTC) residents whereas ST131-C2 clustered in a specific North East (NE) Calgary sector comprising of six neighbourhoods without LTC centres. This NE sector has high immigration and travel rates from the Indian subcontinent. CONCLUSIONS: This study showed that ST131 C subclades have different geographical distribution patterns in Calgary. We believe that recent travel to and immigration from certain high-risk regions for antimicrobial resistance are responsible for the ST131-C2 NE Calgary clustering pattern.

Trends in Population Dynamics of Escherichia coli Sequence Type 131, Calgary, Alberta, Canada, 2006-20161.

Global expansion of antimicrobial drug-resistant Escherichia coli sequence type (ST) 131 is unrivaled among human bacteria. Understanding trends among ST131 clades will help with designing prevention strategies. We screened E. coli from blood samples (n = 1,784) obtained in Calgary, Alberta, Canada, during 2006, 2012, and 2016 by PCR for ST131 and positive samples (n = 344) underwent whole-genome sequencing. The incidence rate per 100,000 residents increased from 4.91 during 2006 to 12.35 during 2012 and 10.12 during 2016. ST131 belonged to clades A (10%), B (9%), and C (81%). Clades C1-nonM27 and B were common during 2006, and C2 containing blaCTX-M-15, C1-M27 containing blaCTX-M-27, and A were responsible for the increase of ST131 during 2012 and 2016. C2 was the most antimicrobial drug-resistant subclade and increased exponentially over time. Eradicating ST131, more specifically the C2 subclade, will lead to considerable public health benefits for persons in Calgary.

A Comprehensive Account of Escherichia coli Sequence Type 131 in Wastewater Reveals an Abundance of Fluoroquinolone-Resistant Clade A Strains.

In the ten years since its discovery, the Escherichia coli clone sequence type 131 (ST131) has become a major international health threat, with the multidrug-resistant and extended-spectrum ß-lactamase (ESBL)-producing clade C emerging as the globally dominant form. ST131 has previously been isolated from wastewater; however, most of these studies selectively screened for ESBL-producing organisms, thereby missing the majority of remaining ST131 clades. In this study, we used a high-throughput PCR-based screening strategy to comprehensively examine wastewater for the presence of ST131 over a 1-year period. Additional multiplex PCRs were used to differentiate clades and obtain an unbiased account of the total ST131 population structure within the collection. Furthermore, antimicrobial susceptibility profiles of all ST131-positive samples were tested against a range of commonly used antibiotics. From a total of over 3,762 E. coli wastewater samples, 1.86% (n = 70) tested positive for ST131, with the majority being clade A isolates. In total, 63% (n = 44) were clade A, 29% (n = 20) were clade B, 1% (n = 1) were clade C0, 6% (n = 4) were clade C1, and 1% (n = 1) were clade C2. In addition, a very high rate of resistance to commonly used antibiotics among wastewater isolates is reported, with 72.7% (n = 32) of clade A resistant to ciprofloxacin and high rates of resistance to gentamicin, sulfamethoxazole-trimethoprim, and tetracycline in clades that are typically sensitive to antibiotics.IMPORTANCE ST131 is a global pathogen. This clone causes urinary tract infections and is frequently isolated from human sources. However, little is known about ST131 from environmental sources. With the widely reported increase in antibiotic concentrations found in wastewater, there is additional selection pressure for the emergence of antibiotic-resistant ST131 in this niche. The unbiased screening approach reported herein revealed that previously antibiotic-sensitive lineages of ST131 are now resistant to commonly used antibiotics present in wastewater systems and may be capable of surviving UV sterilization. This is the most comprehensive account of ST131 in the wastewater niche to date and an important step in better understanding the ecology of this global pathogen.

Sex-hormone-driven innate antibodies protect females and infants against EPEC infection.

Females have an overall advantage over males in resisting Gram-negative bacteremias, thus hinting at sexual dimorphism of immunity during infections. Here, through intravital microscopy, we observed a sex-biased difference in the capture of blood-borne bacteria by liver macrophages, a process that is critical for the clearance of systemic infections. Complement opsonization was indispensable for the capture of enteropathogenic Escherichia coli (EPEC) in male mice; however, a faster complement component 3-independent process involving abundant preexisting antibodies to EPEC was detected in female mice. These antibodies were elicited predominantly in female mice at puberty in response to estrogen regardless of microbiota-colonization conditions. Estrogen-driven antibodies were maternally transferrable to offspring and conferred protection during infancy. These antibodies were conserved in humans and recognized specialized oligosaccharides integrated into the bacterial lipopolysaccharide and capsule. Thus, an estrogen-driven, innate antibody-mediated immunological strategy conferred protection to females and their offspring.

Genomic characterization of IMP and VIM carbapenemase-encoding transferable plasmids of Enterobacteriaceae.

Objectives: IMP and VIM carbapenemases, in association with class 1 integrons, have spread globally among multiple Enterobacteriaceae species. We characterized IMP- and VIM-encoding transferable plasmids of clinical Enterobacteriaceae collected from two global surveillance programmes. Methods: We performed conjugation and transformation experiments for 38 IMP and 89 VIM producers. Plasmids, obtained from transconjugants or transformants, were sequenced with Illumina next-generation sequencing and analysed for replicon types and antimicrobial resistance genes. Results: A total of 41 transconjugants (blaIMP, n = 22; blaVIM, n = 19) and 10 transformants (blaIMP, n = 1; blaVIM, n = 9) were obtained. Broad-host-range IncL/M, IncC and IncN plasmids were associated with blaIMP and blaVIM, contained various integrons and showed inter-species and international distribution. Narrow-host-range IncFII(K) plasmids were limited to Klebsiella pneumoniae with blaIMP-26 from the Philippines, while IncR and IncHI1B-IncFIB(Mar) plasmids were restricted to K. pneumoniae with blaVIM from Greece and Spain. IncA-like hybrid plasmids were detected in Enterobacter xiangfangensis from Italy and K. pneumoniae from Spain. Transferable plasmids were major contributors of antimicrobial resistance genes among Enterobacteriaceae with blaIMP and blaVIM. Conclusions: This is the first report, to the best of our knowledge, describing blaIMP on IncFII(K) plasmids and blaVIM on IncL/M, IncN2, IncHI1B-IncFIB(Mar) and IncX3-IncC-like plasmids and showed that broad-host-range and narrow-host-range plasmids have contributed to the global spread of blaIMP and blaVIM among different species. This study highlights the importance of molecular analysis of plasmids in providing insight into horizontal spread of these carbapenemases.

The population structure of clinical extra-intestinal Escherichia coli in a teaching hospital from Nigeria.

Limited information is available regarding the population structure of extra-intestinal pathogenic Escherichia coli (ExPEC) in Africa. Antimicrobial resistance profiles, sequence types (STs) and fimH types were determined on 60 clinical ExPEC from Nigeria using a 7-single nucleotide polymorphism quantitative PCR and sequencing of certain genes. Different ST131 clades were identified with a multiplex PCR. The isolates were mostly obtained from urines (58.3%). Not-susceptibility rates were as follows: trimethoprim-sulfamethoxazole (98%), cefotaxime (68%), gentamicin (55%), ciprofloxacin (62%) and piperacillin-tazobactam (2%). Dominant STs were associated with CTX-M-15 and included ST131-fimH30 (23%), ST457-fimH145 (20%), ST405-fimH27 (13%) and ST95-fimH41 (10%). We found the 7-SNP qPCR to be simple and cost-effective that can be utilized to tract different ExPEC clones on a global scale. This study provided insight into the population structure of ExPEC from Nigeria showing high prevalence of the rarely reported ST457 and the presence of multidrug resistant ST95.

Rapid Identification of Different Escherichia coli Sequence Type 131 Clades.

Escherichia coli sequence type 131 (ST131) is a pandemic clonal lineage that is responsible for the global increase in fluoroquinolone resistance and extended-spectrum-ß-lactamase (ESBL) producers. The members of ST131 clade C, especially subclades C2 and C1-M27, are associated with ESBLs. We developed a multiplex conventional PCR assay with the ability to detect all ST131 clades (A, B, and C), as well as C subclades (C1-M27, C1-nM27 [C1-non-M27], and C2). To validate the assay, we used 80 ST131 global isolates that had been fully sequenced. We then used the assay to define the prevalence of each clade in two Japanese collections consisting of 460 ESBL-producing E. coli ST131 (2001-12) and 329 E. coli isolates from extraintestinal sites (ExPEC) (2014). The assay correctly identified the different clades in all 80 global isolates: clades A (n = 12), B (n = 12), and C, including subclades C1-M27 (n = 16), C1-nM27 (n = 20), C2 (n = 17), and other C (n = 3). The assay also detected all 565 ST131 isolates in both collections without any false positives. Isolates from clades A (n = 54), B (n = 23), and C (n = 483) corresponded to the O serotypes and the fimH types of O16-H41, O25b-H22, and O25b-H30, respectively. Of the 483 clade C isolates, C1-M27 was the most common subclade (36%), followed by C1-nM27 (32%) and C2 (15%). The C1-M27 subclade with blaCTX-M-27 became especially prominent after 2009. Our novel multiplex PCR assay revealed the predominance of the C1-M27 subclade in recent Japanese ESBL-producing E. coli isolates and is a promising tool for epidemiological studies of ST131.

Genomic epidemiology of global VIM-producing Enterobacteriaceae.

Background: International data on the molecular epidemiology of Enterobacteriaceae with VIM carbapenemases are limited. Methods: We performed short read (Illumina) WGS on a global collection of 89 VIM-producing clinical Enterobacteriaceae (2008-14). Results: VIM-producing (11 varieties within 21 different integrons) isolates were mostly obtained from Europe. Certain integrons with bla VIM were specific to a country in different species and clonal complexes (CCs) (In 87 , In 624 , In 916 and In 1323 ), while others had spread globally among various Enterobacteriaceae species (In 110 and In 1209 ). Klebsiella pneumoniae was the most common species ( n = 45); CC147 from Greece was the most prevalent clone and contained In 590 -like integrons with four different bla VIM s. Enterobacter cloacae complex was the second most common species and mainly consisted of Enterobacter hormaechei ( Enterobacter xiangfangensis , subsp. steigerwaltii and Hoffmann cluster III). CC200 (from Croatia and Turkey), CC114 (Croatia, Greece, Italy and the USA) and CC78 (from Greece, Italy and Spain) containing bla VIM-1 were the most common clones among the E. cloacae complex. Conclusions: This study highlights the importance of surveillance programmes using the latest molecular techniques in providing insight into the characteristics and global distribution of Enterobacteriaceae with bla VIM s.

Urinary Tract Infections among HIV-Positive Pregnant Women in Mwanza City, Tanzania, Are High and Predicted by Low CD4+ Count.

Introduction. Urinary tract infection (UTI) among pregnant women can lead to adverse maternal and foetal outcomes. UTI has been widely studied in the general obstetric population in Tanzania; the present study evaluated the magnitude, antimicrobial resistance, and predictors of UTI among HIV-positive pregnant women. Methods. Between March and May 2016 midstream urine samples from 234 women attending prevention of mother to child transmission of HIV (PMTCT) clinics were analyzed using standard methods. Data was analyzed by STATA version 11.0. Results. The prevalence of UTI was 21.4%, 50/234 [95% CI: 16.1-26.6]. The asymptomatically significant bacteriuria was higher than symptomatically significant bacteriuria (16.6% versus 4.7%, p < 0.001). On multivariable logistic regression analysis, single marital status (OR: 2.6, 95% CI: 1.1-6.1, and p = 0.026), low CD4+ counts of <200/µL (OR: 2.9, 95% CI: 1.1-7.7, and p = 0.031), and having UTI symptoms (OR: 2.5, 95% CI: 1.1-6.0, and p = 0.03) were independent predictors of UTI. Escherichia coli predominated (57.7%) and exhibited a low prevalence of resistance to nitrofurantoin (16.7%), gentamicin (10.0%), and ceftriaxone (13.3%). Four (13.3%) of these were extended-spectrum beta-lactamase producers. Conclusions. A considerable proportion of HIV-positive pregnant women in Mwanza have significant bacteriuria which calls for the need to introduce routine UTI screening at PMTCT clinics to guide specific treatment and prevent associated complications.

Escherichia coli ST131: a multidrug-resistant clone primed for global domination.

A single extra-intestinal pathogenic Escherichia coli (ExPEC) clone, named sequence type (ST) 131, is responsible for millions of global antimicrobial-resistant (AMR) infections annually. Population genetics indicate that ST131 consists of different clades (i.e. A, B, and C); however, clade C is the most dominant globally. A ST131 subclade, named C1-M27, is emerging in Japan and has been responsible for the recent increase in AMR ExPEC in that country. The sequential acquisition of several virulence and AMR genes associated with mobile genetic elements during the 1960s to 1980s primed clade C (and its subclades C1 and C2) for success in the 1990s to 2000s. IncF plasmids with F1:A2:B20 and F2:A1:B replicons have shaped the evolution of the C1 and C2 subclades. It is possible that ST131 is a host generalist with different accessory gene profiles. Compensatory mutations within the core genome of this clone have counterbalanced the fitness cost associated with IncF plasmids. ST131 clade C had dramatically changed the population structure of ExPEC, but it still remains unclear which features of this clade resulted in one of the most unprecedented AMR successes of the 2000s.

Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae.

International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific blaIMP-containing integrons (In809 with blaIMP-4, In722 with blaIMP-6, and In687 with blaIMP-14) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with blaIMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae (n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with blaIMP-26 and In1321 with blaIMP-6 The Enterobacter cloacae complex (n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with blaIMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with blaIMP genes.