Salmonella enterica serovar Infantis is the fifth most common Salmonella serovar isolated in England and Wales. Epidemiological, genotyping and antimicrobial-resistance data for S . enterica Infantis isolates were used to analyse English and Welsh demographics over a 5 year period. Travel cases associated with S . enterica Infantis were mainly from Asia, followed by cases from Europe and North America. Since 2000, increasing numbers of S . enterica Infantis had multidrug resistance determinants harboured on a large plasmid termed ‘plasmid of emerging S . enterica Infantis’ (pESI). Between 2013 and 2018, 42 S . enterica Infantis isolates were isolated from humans and food that harboured resistance determinants to multiple antimicrobial classes present on a pESI-like plasmid, including extended-spectrum β-lactamases (ESBLs; bla CTX-M-65 ). Nanopore sequencing of an ESBL-producing human S . enterica Infantis isolate indicated the presence of two regions on an IncFIB pESI-like plasmid harbouring multiple resistance genes. Phylogenetic analysis of the English and Welsh S . enterica Infantis population indicated that the majority of multidrug-resistant isolates harbouring the pESI-like plasmid belonged to a single clade maintained within the population. The bla CTX-M-65 ESBL isolates first isolated in 2013 comprise a lineage within this clade, which was mainly associated with South America. Our data, therefore, show the emergence of a stable resistant clone that has been in circulation for some time in the human population in England and Wales, highlighting the necessity of monitoring resistance in this serovar.
Abstract Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed animal populations. We conducted whole genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in South West England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identified bla CTX-M (131 isolates: encoding CTX-M-1, −14, −15, −32 and the novel variant, CTX-M-214), bla CMY-2 (6 isolates) and bla DHA-1 (one isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ~220 kb IncHI2 plasmid carrying bla CTX-M-32 was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1500 square kilometres. However, the plasmid was not found amongst human urinary E. coli we have recently characterised from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two bla CTX-M plasmids circulating amongst eight human and two cattle isolates, and a closely related bla CMY-2 plasmid found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found. Importance Third-generation cephalosporins (3GCs) are critically important antibacterials and 3GC-resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli . There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission (e.g. via interaction of people with the local near-farm environment). We characterised acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. Whilst there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids – including one epidemic plasmid that has a remarkable capacity to transmit – there was no evidence that 3GC-R found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population.
ABSTRACT Background Salmonella enterica serovar Agona ( S. Agona) has been increasingly recognised as a prominent cause of gastroenteritis. This serovar is a strong biofilm former that can undergo genome rearrangement and enter a viable but non-culturable state whilst remaining metabolically active. Similar strategies are employed by S. Typhi, the cause of typhoid fever, during human infection, which are believed to assist with the transition from acute infection to chronic carriage. Here we report S. Agona’s ability to persist in people and examine factors that might be contributing to chronic carriage. Methods A review of 2,233 S. Agona isolates from UK infections (2004-2020) and associated carriage was undertaken, in which 1,155 had short-read sequencing data available. A subset of 207 isolates was selected from different stages of acute and persistent infections within individual patients. The subset underwent long-read sequencing and genome structure (GS) analysis, as well as phenotyping assays including carbon source utilisation and biofilm formation. Associations between genotypes and phenotypes were investigated to compare acute infections to those which progress to chronic. Results GS analysis revealed the conserved arrangement GS1.0 in 195 isolates, and 8 additional GSs in 12 isolates. These rearranged isolates were typically associated with early, convalescent carriage (3 weeks – 3 months). We also identified an increase in SNP variation during this period of infection. Conclusion We believe this increase in genome-scale and SNP variation reflects a population expansion after acute S. Agona infection, potentially reflecting an immune evasion mechanism which enables persistent infection to become established.
Supplementary Material for ‘Characterisation of a pESI-like plasmid and analysis of multi-drug resistant S. Infantis isolates in England and Wales’ as published in Microbial Genomics.
Abstract Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales . Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In 37 have been “harvested” by insertion sequence IS 26 as a transposon that is already globally disseminated among the Enterobacterales . This transposon encodes the enzymes AAC(6’)-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from, three hospitals serving a population of 1.5 million people in South West England, we show that increased enzyme production due to mutation in an IS 26 /In 37 -derived hybrid promoter or, more commonly, transposon copy number amplification is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.
Non-typhoidal Salmonella (NTS)infections are associated with high morbidity and mortality. β-lactams are used as first-line treatment but resistance to these has increased considerably in recent years. Azithromycin and fosfomycin are used as alternatives; however, the incidence of resistance in these drugs is also increasing. Epidemiological surveillance on 35,372 NTS received by Public Health England was conducted for analysis of demographics, including global travel. Genomic typing and antimicrobial resistance data for Salmonellaisolates were used to determine the prevalence of β-lactam, azithromycin and fosfomycin resistance in NTSover a four year period. No isolates were resistant to β-lactams, azithromycin or fosfomycin alone but all isolates were resistant to multiple antimicrobial classes. IncHI2, IncY and IncN plasmids were predominantly found in the most multi-drug resistant isolates. Multi-drug resistance (MDR) was particularly a concern in the S. Infantis population. Therefore, long read sequencing was used to characterise an MDR S. Infantis isolate. Three drug regions were identified in a IncFIB, a mega plasmid identified in this isolate. The resistance determinants fosA, arsA, arsD and blaCTXM65,were discovered on the same drug region. Analysis of IncFIB in this S.Infantis isolate revealed 99% similarity to a IncFIB plasmid in S. Infantis isolated from chickens in the USA. Thishas not been reported before, warranting efforts for enhanced surveillance programmes to identify sources of emerging resistance, which will aid in establishing control measures for prevention of spread of resistance.
Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales . Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In 37 have been “harvested” by insertion sequence IS 26 as a transposon that is widely disseminated among the Enterobacterales . This transposon encodes the enzymes AAC(6’)-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS 26 /In 37 -derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
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