Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

Abstract

Multi-drug resistant (MDR), gram-negative Enterobacteriaceae, such as Escherichia coli (E. coli) limit therapeutic options and increase morbidity, mortality, and treatment costs worldwide. They pose a serious burden on healthcare systems, especially in developing countries like Rwanda. Several studies have shown the effects caused by the global spread of extended-spectrum beta-lactamase (ESBL)-producing E. coli. However, limited data is available on transmission dynamics of these pathogens and the mobile elements they carry in the context of clinical and community locations in Sub-Saharan Africa. Here, we examined 120 ESBL-producing E. coli strains from patients hospitalized in the University Teaching Hospital of Butare (Rwanda), their attending caregivers as well as associated community members and livestock. Based on whole-genome analysis, the genetic diversification and phylogenetics were assessed. Moreover, the content of carried plasmids was characterized and investigated for putative transmission among strains, and for their potential role as drivers for the spread of antibiotic resistance. We show that among the 30 different sequence types (ST) detected were the pandemic clonal lineages ST131, ST648 and ST410, which combine high-level antimicrobial resistance with virulence. In addition to the frequently found resistance genes blaCTX–M–15, tet(34), and aph(6)-Id, we identified csg genes, which are required for curli fiber synthesis and thus biofilm formation. Numerous strains harbored multiple virulence-associated genes (VAGs) including pap (P fimbriae adhesion cluster), fim (type I fimbriae) and chu (Chu heme uptake system). Furthermore, we found phylogenetic relationships among strains from patients and their caregivers or related community members and animals, which indicates transmission of pathogens. Also, we demonstrated the presence and potential transfer of identical/similar ESBL-plasmids in different strains from the Rwandan setting and when compared to an external plasmid. This study highlights the circulation of clinically relevant, pathogenic ESBL-producing E. coli among patients, caregivers and the community in Rwanda. Combining antimicrobial resistance with virulence in addition to the putative exchange of mobile genetic elements among bacterial pathogens poses a significant risk around the world.

Molecular Epidemiology of Extended-Spectrum Beta-Lactamase and AmpC Producing Enterobacteriaceae among Sepsis Patients in Ethiopia: A Prospective Multicenter Study

“…Bla CTX-M-15 (70.4%) was the most abundant ESBL gene detected. This finding showed similarities with different studies across the globe [ 1 , 14 , 20 , 27 , 29 , 32 ]. Bla CTX-M-15 was very abundant at TASH (73.6%) and HUCSH (93%), while it was detected at a comparatively lower rate at DRH (50.4%).…”

“…Some key families of ESBL-encoding genes, such as bla CTX-M , bla TEM and bla SHV are grouped in class A [ 8 , 12 , 13 ]. The bla CTX-M family, that spread rapidly during the last decade, originated from environmental bacteria and its variants have developed due to point mutations [ 14 ]. All bla CTX-M variants are ESBL genes [ 8 , 13 ] in which bla CTX-M-15 is presently the most prevalent [ 10 ].…”

Highly Virulent and Multidrug-Resistant Escherichia coli Sequence Type 58 from a Sausage in Germany

“…A growing body of studies shows the global spread of MDR E. coli and underlines the clinical relevance of this pathogen, with nearly 60,000 deaths caused by antibiotic-resistant E. coli in 2019 alone [ 28 ]. In addition, MDR E. coli strains are commonly found in the environment, in animals (pets and livestock), and in meat products [ 2 , 29 , 30 , 31 , 32 , 33 , 34 ]. Due to increasing worldwide meat consumption and pressure on the prices of processed foods, slaughterhouses have to operate in an economically-oriented high throughput, potentially leading to the contamination of meat products and the water used with enteric pathogens of animal origin [ 35 ].…”

Extensively Drug-Resistant Klebsiella pneumoniae Counteracts Fitness and Virulence Costs That Accompanied Ceftazidime-Avibactam Resistance Acquisition

“…Several pandemic high-risk clonal lineages have been identified in recent years, which successfully combine high-level virulence and resilience ( 1 , 103 – 107 ) with extensive drug resistance, even in more pristine environments with low antibiotic selection pressures ( 108 – 110 ). This combination and the nonreversibility of resistance could be due to different compensatory events that counteract fitness costs ( 111 ).…”