SXT/R391 integrative and conjugative elements in Proteus species reveal abundant genetic diversity and multidrug resistance

Abstract

SXT/R391 integrative and conjugative elements (ICEs) are self-transmissible mobile genetic elements that are found in most members of Enterobacteriaceae. Here, we determined fifteen SXT/R391 ICEs carried by Proteus isolates from food (4.2%) and diarrhoea patients (17.3%). BLASTn searches against GenBank showed that the fifteen SXT/R391 ICEs were closely related to that from different Enterobacteriaceae species, including Proteus mirabilis. Using core gene phylogenetic analysis, the fifteen SXT/R391 ICEs were grouped into six distinct clusters, including a dominant cluster and three clusters that have not been previously reported in Proteus isolates. The SXT/R391 ICEs shared a common structure with a set of conserved genes, five hotspots and two variable regions, which contained more foreign genes, including drug-resistance genes. Notably, a class A β-lactamase gene was identified in nine SXT/R391 ICEs. Collectively, the ICE-carrying isolates carried resistance genes for 20 tested drugs. Six isolates were resistant to chloramphenicol, kanamycin, streptomycin, trimethoprim-sulfamethoxazole, sulfisoxazole and tetracycline, which are drug resistances commonly encoded by ICEs. Our results demonstrate abundant genetic diversity and multidrug resistance of the SXT/R391 ICEs carried by Proteus isolates, which may have significance for public health. It is therefore necessary to continuously monitor the antimicrobial resistance and related mobile elements among Proteus isolates.

Genetics of Acquired Antibiotic Resistance Genes in Proteus spp.

“…Integrative conjugative elements are auto-transferable mobile genetic elements that can be excised from the chromosome via their integrase/excisionase gene of the host bacterium and form a circular intermediate that can be transferred by conjugation (Li et al, 2016). The ICE SXT/R391 family is one of the largest ICE families with the most abundant diversity among Gramnegative bacterial species.…”

“…They carry genes coding for the resistance to sulfamethoxazole, trimethoprim, chloramphenicol, mercury, streptomycin and kanamycin, as well as β-lactamases genes [bla HMS−1 (Ryan et al, 2017), bla CMY−2 (Harada et al, 2010), bla CTX−M−2 (Mata et al, 2011)]. SXT/R391-type ICEs have been identified in strains of P. mirabilis not only in Asia (Li et al, 2016) but also in Spain (Mata et al, 2011) and in France (Aberkane et al, 2016). They are easily transferable by conjugation of P. mirabilis to E. coli, K. pneumoniae, Salmonella enterica serovar Typhimurium, or Citrobacter koseri (Harada et al, 2010) (Figures 2, 3).…”

Molecular Analysis, Biochemical Characterization, Antimicrobial Activity, and Immunological Analysis of Proteus mirabilis Isolated from Broilers

“…Since the extended‐spectrum β‐lactamse genes were detected in P. mirabilis in 1987 (Malekjamshidi et al., ), this multi‐antibiotic resistant bacterium has been isolated in poultry in recent years (Aragón et al., ; Lei et al., ; Li et al., ; Tonkic et al., ). The detection of many extended‐spectrum β‐lactamse genes from our isolates, which is in agreement with the results from others (Barbour et al., ; Reich et al., ; Wong et al., ), implies that the extended‐spectrum β‐lactamse genes are common in P. mirabilis isolates from poultry and may pose potential threats on public health.…”

“…Recently, P. mirabilis has been frequently isolated from food‐producing animals, including poultry (for example, Barbour et al., ; Kim, Wei, & An, ; Lei et al., , ; Nyenje and others ; Olonitola, Fahrenfeld, & Pruden, ; Reich, Atanassova, & Klein, ; Wong, Wan, & Chen, ). Several reports have shown that this bacterium can cause foodborne illness in humans (Shi et al., ; Wang et al., ).…”

“…Several reports have shown that this bacterium can cause foodborne illness in humans (Shi et al., ; Wang et al., ). Because the discovery of extended‐spectrum β‐lactamase Proteus in 1987 that is a serious public health issue worldwide (Malekjamshidi, Shahcheraghi, & Feizabadi, ), multi‐antibiotic resistant Proteus has been documented in the recent years (for example, Aragón et al., ; Lei et al., ; Li et al., ; Tonkic et al., ). The reasons of the emergence of antibiotic resistant Proteus isolated from food animals are not clear (Tumbarello et al., ; Wong et al., ).…”