Abstract
Antimicrobial resistance (AMR) is currently one of the most important challenges to the treatment of bacterial infections. A critical issue to combat AMR is to restrict its spread. In several instances, bacterial plasmids are involved in the global spread of AMR. Plasmids belonging to the incompatibility group (Inc)HI are widespread in Enterobacteriaceae and most of them express multiple antibiotic resistance determinants. They play a relevant role in the recent spread of colistin resistance. We present in this report novel findings regarding IncHI plasmid conjugation. Conjugative transfer in liquid medium of an IncHI plasmid requires expression of a plasmid-encoded, large-molecular-mass protein that contains an Ig-like domain. The protein, termed RSP, is encoded by a gene (ORF R0009) that maps in the Tra2 region of the IncHI1 R27 plasmid. The RSP protein is exported outside the cell by using the plasmid-encoded type IV secretion system that is also used for its transmission to new cells. Expression of the protein reduces cell motility and enables plasmid conjugation. Flagella are one of the cellular targets of the RSP protein. The RSP protein is required for a high rate of plasmid transfer in both flagellated and nonflagellated Salmonella cells. This effect suggests that RSP interacts with other cellular structures as well as with flagella. These unidentified interactions must facilitate mating pair formation and, hence, facilitate IncHI plasmid conjugation. Due to its location on the outer surfaces of the bacterial cell, targeting the RSP protein could be a means of controlling IncHI plasmid conjugation in natural environments or of combatting infections caused by AMR enterobacteria that harbor IncHI plasmids.
Highlights
Infectious diseases, despite the availability of antibiotics, remain an important public health issue, representing the second leading cause of death worldwide [1]
Dissemination of antimicrobial resistance (AMR) among different bacterial populations occurs due to mainly the presence of plasmids that encode Antimicrobial resistance (AMR) determinants
Considering that IncHI plasmids significantly contribute to AMR dissemination within enterobacteria, the findings reported in this paper suggest that the identified protein can be a target to control both IncHI-mediated AMR dissemination and infections caused by AMR enterobacteria that harbor these plasmids
Summary
Infectious diseases, despite the availability of antibiotics, remain an important public health issue, representing the second leading cause of death worldwide [1]. The gradual increase in resistance rates of several important pathogens represents a serious threat to public health [2,3,4]. Plasmids belonging to the incompatibility group (Inc) HI include mainly genetic elements encoding AMR determinants [8] and are widespread in Enterobacteriaceae. Within the genus Salmonella, IncHI plasmids account for a significant proportion of antibiotic resistance phenotypes in the most common invasive Salmonella serovars: S. enterica serovar Typhi and S. Typhi strains has shown that more than 40% of all isolates harbor an IncHI plasmid [13]. A recent study has shown that IncHI2 plasmids predominate in antibiotic-resistant Salmonella isolates [14]. IncHI-encoded AMR can be present in other enterobacterial genera, such as Klebsiella pneumoniae [15] and Citrobacter freundii [16]
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