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1.
Microbiol Spectr ; 11(6): e0178423, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37819128

ABSTRACT

IMPORTANCE: Diseases caused by Enterobacteriaceae multidrug-resistant strains have become increasingly difficult to manage. It is necessary to verify the new antibacterial drug MccY effect on non-typhoid Salmonella infection in mice since it is regarded as a promising microcin. The results demonstrated that MccY has a potential therapeutic application value in the protection against Salmonella-induced intestinal damage and alleviating related intestinal dysbiosis and metabolic disorders. MccY could be a promising candidate as an antimicrobial or anti-inflammatory agent for treating infectious diseases.


Subject(s)
Gastrointestinal Microbiome , Mice , Animals , Intestinal Barrier Function , Inflammation/drug therapy , Salmonella , Peptides , Dysbiosis/microbiology
2.
Microbiol Spectr ; 10(6): e0185922, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36453909

ABSTRACT

Salmonella bacteria pose a significant threat to animal husbandry and human health due to their virulence and multidrug resistance. The lasso peptide MccY is a recently discovered antimicrobial peptide that acts against various serotypes of Salmonella. In this study, we further explore the resistance mechanism and activity of MccY. Mutants of Ton system genes, including tonB, exbB, and exbD, in Salmonella enterica subsp. enterica serovar Typhimurium were constructed, and the MICs to MccY exhibited significant increases in these deletion mutants compared to the MIC of the parent strain. Subsequently, MccY resistance was quantitatively analyzed, and these mutants also showed greatly reduced rates of killing, even with a high concentration of MccY. In addition, a minimal medium with low iron environment enhanced the sensitivity of these mutants to MccY. Measurements of a series of physiological indicators, including iron utilization, biofilm formation, and motility, demonstrated that MccY may decrease the virulence of S. Typhimurium. Transcriptomic analysis showed that iron utilization, biofilm formation, flagellar assembly, and virulence-related genes were downregulated to varying degrees when S. Typhimurium was treated with MccY. In conclusion, deletion of Ton system genes resulted in resistance to MccY and the susceptibility of these mutants to MccY was increased and differed under a low-iron condition. This lasso peptide can alter multiple physiological properties of S. Typhimurium. Our study will contribute to improve the knowledge and understanding of the mechanism of MccY resistance in Salmonella strains. IMPORTANCE The resistance of Salmonella to traditional antibiotics remains a serious challenge. Novel anti-Salmonella drugs are urgently needed to address the looming crisis. The newly identified antimicrobial peptide MccY shows broad prospects for development and application because of its obvious antagonistic effect on various serotypes of Salmonella. However, our previous study showed that the peptide could confer resistance to Salmonella by disrupting the receptor gene fhuA. In this study, we further explored the potential resistance mechanism of MccY and demonstrated the importance of the Salmonella Ton complex for MccY transport. Disruption in Ton system genes resulted in S. Typhimurium resistance to this peptide, and MccY could alter multiple bacterial physiological properties. In summary, this study further explored the resistance mechanism and antibacterial effect of MccY in S. Typhimurium and provided a scientific basis for its development and application.


Subject(s)
Anti-Bacterial Agents , Bacteriocins , Salmonella enterica , Salmonella typhimurium , Anti-Bacterial Agents/pharmacology , Salmonella enterica/drug effects , Salmonella enterica/genetics , Salmonella typhimurium/drug effects , Serogroup , Bacteriocins/pharmacology
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