Biology subjects

Petrovska, L.

Publications and source records attributed to Petrovska, L..

5 recordsLinked to original sources

bioRxiv2024

Reversible excision of the wzy locus in Salmonella Typhimurium may aid recovery following phage predation

Bacteriophage (phage) are promising novel antimicrobials but a key challenge to their effective implementation is the rapid emergence of phage resistance. An improved understanding of phage-host interactions is therefore needed. The Anderson phage typing scheme differentiates closely related strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) based on sensitivity to a panel of phage preparations. Switches in phage type are indicative of changes in phage sensitivity and inform on the dynamics of phage interaction with their host bacteria. We investigated the molecular basis of switches between the relatively phage sensitive S. Typhimurium DT8 and phage resistant DT30 strains that are present in the same phylogenetic clade. DT30 strains emerged from DT8 strains predominantly by deletion of a genomic region affecting the wzy locus encoding an O-antigen polymerase. The deletion site was flanked by two perfect direct repeats designated attL and attR. During broth culture in the presence of a typing phage that used O-antigen as primary receptor the {Delta}wzy genotype increased in frequency compared with culture in the absence of phage and removal of attL prevented deletion of the wzy locus. Co-culture of S. Typhimurium DT8 with a strain lacking wzy resulted in reversion of the latter to wild type. We propose a model in which reversible deletion of the wzy locus enables recovery of S. Typhimurium DT8 following predation by phage that use O-antigen as their primary receptor. This was consistent with ancestral state reconstruction of DT8 and DT30 phylogeny that supported a model of reversible transition from DT8 to DT30 in natural populations. ImportanceS. Typhimurium is a major pathogen of livestock that adversely affects productivity and animal welfare and poses a risk of foodborne disease in the human population. Antibiotics are used to control Salmonella infections in livestock that contributes to the antimicrobial resistance global emergency. Viruses of bacteria (phage) are one alternative to antibiotics to control Salmonella in the food chain but their successful implementation as antimicrobials is restricted by the rapid emergence of resistance to phage. A better understanding of the outcome of phage-bacteria interactions is needed to optimise the design and implementation of phage-based antimicrobials. This study identifies a genetic mechanism that confers resistance to phage that use O-antigen as a receptor on the surface of Salmonella. The mechanism is likely to impart a fitness cost on the bacterium but importantly the mechanism has the potential to be revert to a fully fit state once phage predation ceases. A model for how the mechanism may contribute to survival and recovery following phage predation is proposed.

microbiology↗

bioRxiv2023

Salmonella Infantis, the emerging human multidrug resistant pathogen - a One Health perspective

Salmonella Infantis presents an ever-increasing threat to public health due to its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). Whole genome sequences of 5,284 S. Infantis strains from 74 countries, isolated between 1989 and 2020 from a wide variety of sources including humans, animals, and food, were analysed to compare genetic phylogeny, AMR determinants and plasmid presence. The global S. Infantis population structure diverged into three clusters: a North American cluster, European cluster and a global cluster. The levels of AMR varied between the S. Infantis clusters and by isolation source; 73% of poultry isolates had multidrug resistance (MDR) compared to 35% of human isolates. This correlated with plasmid of emerging S. Infantis (pESI) presence; 71% of poultry isolates contained pESI versus 32% of human isolates. This provides important information for public health teams engaged in reducing the spread of this pathogen.

microbiology↗

bioRxiv2020

Ecological niche adaptation of a bacterial pathogen associated with reduced zoonotic potential

The emergence of new bacterial pathogens is a continuing challenge for agriculture and food safety. Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of foodborne illness worldwide, with pigs a major zoonotic reservoir. Two variants, S. Typhimurium phage type U288 and monophasic S. Typhimurium (S. 4,[5],12:i:-) ST34 emerged and have accounted for the majority of isolates from pigs in the UK in the past two decades, but have distinct host range and risk to food safety. ST34 accounts for over 50% of all S. Typhimurium infections in people while U288 less than 2%. U288 and ST34 form distinct phylogenetic clusters within S. Typhimurium, defined by approximately 600 SNPs within their 5 Mbp genomes. Evolution of the U288 clade from an LT2-like ancestor was characterised by the acquisition of AMR genes, insertions and deletions in the virulence plasmid pU288-1, and the accumulation of polymorphisms, some of which resulted in truncation of coding sequences. U288 isolates exhibited lower growth rate and viability following desiccation compared to ST34 isolates, characteristics that could affect transmission through the food chain. U288 and ST34 isolates exhibited distinct outcomes of infection in the murine model of colitis, and colonised pigs in a manner that affected the disease symptoms and distribution in organs. U288 infection was more disseminated in the lymph nodes while ST34 were recovered in greater numbers in the intestinal contents. These data are consistent with the evolution of S. Typhimurium U288 adaptation to pigs that may determine their reduced zoonotic potential. ImportanceBacterial pathogens continually evolve to exploit new ecological niches as they emerge due to human activity including agricultural, medical or societal practice. The consequences of the emergence of new pathogens may affect outcome of infection and risk to human or animal health. Genome sequence can resolve the population structure, identify variants that are evolving as they enter a new niche, and pinpoint potential functional divergence. We report a variant S. Typhimurium that adapted to a unique niche distinct to that occupied by a second S. Typhimurium variant circulating in the same pig populations. Adaptation was accompanied by phenotypic and genotypic changes consistent with a more invasive lifestyle and a decreased zoonotic potential observed in the epidemiological record. Our findings suggest that pathogen genotypic variation may be useful in estimating zoonotic potential and threat to livestock welfare.

microbiology↗

bioRxiv2019

Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation

Salmonella enterica serotype Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and disseminated disease worldwide. Two S. Typhimurium strains (SL1344 and ATCC14028) are widely used to study host-pathogen interactions, yet genotypic variation results in strains with diverse host range, pathogenicity and risk to food safety. A robust fully parsimonious phylogenetic tree constructed from recombination purged variation in the whole genome sequence of 131 diverse strains of S. Typhimurium revealed population structure composed of two high order clades ( and {beta}) and multiple subclades on extended internal branches, that exhibited distinct signatures of host adaptation and anthropogenic selection. Clade contained a number of subclades composed of strains from well characterized epidemics in domesticated animals, while clade {beta} predominantly contained subclades associated with wild avian species, with the notable exception of a subclade containing the DT204/49 complex. The contrasting epidemiology of and {beta} strains was reflected in a distinct distribution of antimicrobial resistance (AMR) genes, accumulation of hypothetically disrupted coding sequences (HDCS), and signatures of functional diversification associated with invasiveness of host adapted serotypes. Gene flux was predominantly driven by acquisition, loss or recombination of prophage. The acquisition of large genetic islands (SGI-1 and 4) was limited to two recent pandemic clones (DT104 and monophasic S. Typhimurium ST34) in clade . Together, our data are consistent with the view that a broad host range common ancestor of S. Typhimurium diversified with clade lineages remained largely associated with multiple domesticated animal species, while clade {beta} spawned multiple lineages that underwent diversifying selection associated with adaptation to various niches, predominantly in wild avian species.

genomics↗

bioRxiv2019

SGI-4 in monophasic Salmonella Typhimurium ST34 is a novel ICE that enhances resistance to copper

A multi drug resistant (MDR) Salmonella enterica 4,[5],12:i-of sequence type 34 (monophasic S. Typhimurium ST34) is a current pandemic clone associated with livestock and numerous outbreaks in the human population. A large genomic island, termed SGI-4, is present in the monophasic Typhimurium ST34 clade and absent from other S. Typhimurium strains. SGI-4 consists of 78 open reading frames including sil and pco genes previously implicated in resistance to copper and silver, and multiple genes predicted to be involved in mobilisation and transfer by conjugation. SGI-4 was excised from the chromosome, circularised and transferred to recipient strains of S. Typhimurium at a frequency influenced by stress and induced by mitomycin C and oxygen tension. The presence of SGI-4 was associated with increased resistance to copper, particularly but not exclusively under anaerobic conditions. The presence of silCBA genes, predicted to encode an RND family efflux pump that transports copper from the periplasm to the external milieu, was sufficient to impart the observed enhanced resistance to copper. The presence of silCBA genes resulted in the absence of copper-dependent induction of a multicopper oxidase system encoded by pco genes, also present on SGI-4, suggesting that the system effectively limits the copper availability in the periplasm. The presence of silCBA genes did not affect SodCI-dependent macrophage survival.

microbiology↗