The escalating misuse and excessive utilization of antibiotics have led to the widespread dissemination of drug-resistant bacteria, posing a significant global healthcare crisis. Of particular concern is the increasing prevalence of multi-drug resistant (MDR) opportunistic pathogens in Intensive Care Units (ICUs), which presents a severe threat to public health and contributes to substantial morbidity and mortality. Among them, MDR ESKAPE pathogens account for the vast majority of these opportunistic pathogens. This comprehensive review provides a meticulous analysis of the current prevalence landscape of MDR opportunistic pathogens in ICUs, especially in ESKAPE pathogens, illuminating their resistance mechanisms against commonly employed first-line antibiotics, including polymyxins, carbapenems, and tigecycline. Furthermore, this review explores innovative strategies aimed at preventing and controlling the emergence and spread of resistance. By emphasizing the urgent need for robust measures to combat nosocomial infections caused by MDR opportunistic pathogens in ICUs, this study serves as an invaluable reference for future investigations in the field of antibiotic resistance.

Salmonella are a type of bacteria known to cause food-borne illness. Their host range varies widely, and their susceptibility to the host determines its pathogenicity. Salmonellaenterica serovar Rissen (S. Rissen) is a widely distributed serotype; however, its virulence and pathogenicity are poorly understood. In this study, the pathogenicity and antibiotic resistance of a representative S. Rissen isolate were investigated. The cell model results showed that S. Rissen preferred to replicate in human macrophage cells U937 compared to murine macrophage cells RAW264.7, suggesting that it has a level of host adaptability. Genome sequencing and comparison analysis revealed that the distribution and nonsynonymous single nucleotide polymorphisms of virulence factors in S. Rissen were similar to those in S. Typhi rather than to those in S. Typhimurium. Taken together, our results suggest that although S. Rissen is a common serotype distributed in swine herds, pork and chicken products, it has strong ability to infect humans.

Summary: MCR‐4 and MCR‐8 are two recently identified members of an ongoing MCR family of colistin resistance. Although that aquatic reservoir for MCR‐4 is proposed, the origin and mechanism of MCR‐8 is poorly understood. Here we report a previously unrecognized non‐mobile colistin resistance enzyme, termed NMCR‐2, originating from the plant pathogen Kosakonia pseudosacchari . NMCR‐2 (551aa) gives 67.3% identity to MCR‐8 (565aa). NMCR‐2 is placed as a progenitor/ancestor for MCR‐8 in phylogeny of MCR members. Genetic study reveals that nmcr‐2 is comparable to mcr‐8 in the ability of producing phenotypic colistin resistance. Biochemical analyses determine that these two enzymes catalyse the transfer of PEA from the donor PE lipid substrate to the recipient lipid A molecule by a putative ‘ping‐pong’ trade‐off. Further experiment of protein engineering demonstrates that the two motifs (TM region and catalytic domain) of NMCR‐2 are functionally exchangeable with that of MCR‐8, rather than MCR‐1. Physiological impacts of nmcr‐2 and/or mcr‐8 are detected in Escherichia coli , featuring with fitness cost. Evidently, the action and mechanism of NMCR‐2 is analogous to that of MCR‐8. Therefore, our finding underlines that NMCR‐2 might be a possible progenitor of MCR‐8.