Rough-type and loss of the LPS due to lpx genes deletions are associated with colistin resistance in multidrug-resistant clinical Escherichia coli isolates not harbouring mcr genes

Moosavian, Mojtaba; Emam, Nasrin; Pletzer, Daniel; Savari, Mohammad

doi:10.1371/journal.pone.0233518

Cited by 20 publications

(13 citation statements)

References 39 publications

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“…Furthermore, additional genetic polymorphisms in genes of the two-component system (TCS) (PhoPQ, PmrAB, ParRS, ColRS, CprRS) and their regulators (MgrB, PmrD, PmrC, PmrE and the PmrHFIJKLM operon) involved in lipid A biosynthesis have also been identified as responsible for COL resistance in GNB [ 7 , 10 , 11 , 12 , 13 ]. Mutations in genes and operons essential for the lipid A formation, such as lpxA , lpxC , lpxD , have also been described [ 14 , 15 ]. S. enterica polymyxin-resistance is modulated mainly by substituting the acyl chains, the phosphate groups on the lipid A moiety of LPS and alterations into membrane fluidity/permeability [ 7 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

et al. 2022

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Background: A collection of human-epidemiologically unrelated S. enterica strains collected over a 3-year period (2016 to 2018) in Italy by the national surveillance Enter-Net Italia was analysed. Methods: Antimicrobial susceptibility tests, including the determination of minimal inhibitory concentrations (MICs) for colistin, were performed. Colistin resistant strains were analysed by PCR to detect mobile colistin resistance (mcr) genes. In mcr-negative S. enterica serovar Enteritidis strains, chromosomal mutations potentially involved in colistin resistance were identified by a genomic approach. Results: The prevalence of colistin-resistant S. enterica strains was 7.7%, the majority (87.5%) were S. Enteritidis. mcr genes were identified only in one strain, a S. Typhimurium monophasic variant, positive for both mcr-1.1 and mcr-5.1 genes in an IncHI2 ST4 plasmid. Several chromosomal mutations were identified in the colistin-resistant mcr-negative S. Enteritidis strains in proteins involved in lipopolysaccharide and outer membrane synthesis and modification (RfbN, LolB, ZraR) and in a component of a multidrug efflux pump (MdsC). These mutated proteins were defined as possible candidates for colistin resistance in mcr-negative S. Enteritidis of our collection. Conclusions: The colistin national surveillance in Salmonella spp. in humans, implemented with genomic-based surveillance, permitted to monitor colistin resistance, determining the prevalence of mcr determinants and the study of new candidate mechanisms for colistin resistance.

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Section: Introductionmentioning

confidence: 99%

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

et al. 2022

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“…As observed in the biofilm and adherence and invasion assays, this increase was most pronounced in DS566-2, the strain with the most significant predicted LPS truncation. Other groups have shown an increased resistance to colistin in Gram negative pathogens lacking the lipid A portion of LPS(89, 90). Our phage-driven mutants retain lipid A, explaining their sensitivity to colistin.…”

Section: Discussionmentioning

confidence: 99%

Phage resistance accompanies reduced fitness of uropathogenicE. coliin the urinary environment

Zulk

Clark

Ottinger

et al. 2021

Preprint

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Urinary tract infections (UTIs) are among the most common infections treated worldwide each year and are primarily caused by uropathogenic E. coli (UPEC). Rising rates of antibiotic resistance among uropathogens have spurred consideration of alternative strategies such as bacteriophage (phage) therapy; however, phage-bacterial interactions within the urinary environment are poorly defined. Here, we assess the activity of two phages, HP3 and ES17, against clinical UPEC isolates using in vitro and in vivo models of UTI. In both bacteriologic medium and pooled human urine, we identified phage resistance arising within the first 6-8 hours of coincubation. Whole genome sequencing revealed that UPEC resistant to HP3 and ES17 harbored mutations in genes involved in lipopolysaccharide (LPS) biosynthesis. These mutations coincided with several in vitro phenotypes, including alterations to adherence to and invasion of human bladder epithelial HTB-9 cells, and increased biofilm formation. Interestingly, these phage-resistant UPEC demonstrated reduced growth in pooled human urine, which could be partially rescued by nutrient supplementation, and were more sensitive to several outer membrane targeting antibiotics than parental strains. Additionally, these phage-resistant UPEC were attenuated in a murine UTI model. In total, our findings suggest that while resistance to phages, such as LPS-targeted HP3 and ES17, may readily arise in the urinary environment, phage resistance is accompanied by fitness costs rendering UPEC more susceptible to host immunity or antibiotics.IMPORTANCEUTIs are one of the most common causes of outpatient antibiotic use, and rising antibiotic resistance threatens the ability to control these infections unless alternative treatments are developed. Bacteriophage (phage) therapy is gaining renewed interest, however, much like antibiotics, bacteria can readily become resistant to phage. For successful UTI treatment, we must predict how bacteria will evade killing by phage and identify the downstream consequences of phage-resistant bacterial infections. In our current study, we found that while phage-resistant mutant bacteria quickly emerged, these mutations left bacteria less capable of growing in human urine and colonizing the murine bladder. These results suggest that phage therapy poses a viable UTI treatment if phage resistance confers fitness costs for the uropathogen. These results have implications for developing cocktails of phage with multiple different bacterial targets, each of which is only evaded at the cost of bacterial fitness.

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“…Presence of LPS is characteristic to gram-negative bacteria, and its complete loss is rare. In some bacteria, loss of LPS was suggested to be partially compensated for by the production of other classes of lipids in the outer membrane [ 98 ]. Liberibacter spp.…”

Section: Strategies For Coexistence Within Insect Vectormentioning

confidence: 99%

Interactions of Liberibacter Species with Their Psyllid Vectors: Molecular, Biological and Behavioural Mechanisms

Mishra

Ghanim

2022

IJMS

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Liberibacter is a group of plant pathogenic bacteria, transmitted by insect vectors, psyllids (Hemiptera: Psylloidea), and has emerged as one of the most devastating pathogens which have penetrated into many parts of the world over the last 20 years. The pathogens are known to cause plant diseases, such as Huanglongbing (citrus greening disease), Zebra chip disease, and carrot yellowing, etc., threatening some very important agricultural sectors, including citrus, potato and others. Candidatus Liberibacter asiaticus (CLas), the causative agent of citrus greening disease, is one of the most important pathogens of this group. This pathogen has infected most of the citrus trees in the US, Brazil and China, causing tremendous decline in citrus productivity, and, consequently, a severely negative impact on economic and personnel associated with citrus and related industries in these countries. Like other members in this group, CLas is transmitted by the Asian citrus psyllid (ACP, Diaphorina citri) in a persistent circulative manner. An additional important member of this group is Ca. L. solanacearum (CLso), which possesses nine haplotypes and infects a variety of crops, depending on the specific haplotype and the insect vector species. Ongoing pathogen control strategies, that are mainly based on use of chemical pesticides, lack the necessary credentials of being technically feasible, and environmentally safe. For this reason, strategies based on interference with Liberibacter vector transmission have been adopted as alternative strategies for the prevention of infection by these pathogens. A significant amount of research has been conducted during the last 10-15 years to understand the aspects of transmission of these bacterial species by their psyllid vectors. These research efforts span biological, ecological, behavioural and molecular aspects of Liberibacter–psyllid interactions, and will be reviewed in this manuscript. These attempts directed towards devising new means of disease control, endeavoured to explore alternative strategies, instead of relying on using chemicals for reducing the vector populations, which is the sole strategy currently employed and which has profound negative effects on human health, beneficial organisms and the environment.

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Rough-type and loss of the LPS due to lpx genes deletions are associated with colistin resistance in multidrug-resistant clinical Escherichia coli isolates not harbouring mcr genes

Cited by 20 publications

References 39 publications

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

Phage resistance accompanies reduced fitness of uropathogenicE. coliin the urinary environment

Interactions of Liberibacter Species with Their Psyllid Vectors: Molecular, Biological and Behavioural Mechanisms

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