Antibiotics resistance and regulatory mechanism of virulence expression in salmonella

Abstract

Bacterial infections have become an important public health issue worldwide. Combating bacterial infections has been commonplace in human history. Among various bacterial species, Salmonella enterica is one of the most important human pathogens. In recent years, acquisition of antibiotics resistance genes by clinically important Salmonella strains and invasive infection of high virulence Salmonella has become a global concern. Co-existence of the Transferable Mechanisms of Quinolone Resistance (TMQR) genes oqxAB and aac(6’)-Ib-cr in Salmonella is often associated with expression of fluoroquinolone resistance in this important pathogen. However, Salmonella that carried the plasmid-borne genes (Tn6010-oqxABR) may not express fluoroquinolone-resistance phenotype. The works described in this thesis aimed to investigate the molecular mechanisms underlying regulation of fluoroquinolone susceptibility in Salmonella by the oqxAB genes, and elucidate the global regulatory mechanisms involved in control of expression of plasmid-borne genes. In addition to antibiotics resistance, the works in this thesis also described different virulence-encoding mechanisms in Salmonella. It should be noted that Salmonella is a notorious foodborne pathogen which comprises strains that exhibit varied ability to cause human infection. In previous reports, over-expression of various virulence determination factors was observable in the high virulence Salmonella strains. However, the molecular mechanisms underlying expression of virulence in Salmonella is still poorly defined. This work therefore aimed at elucidating the regulatory networks that underlie expression of virulence phenotypes in Salmonella. In particular, the relationship between the level of double-stranded RNA (dsRNA) and phenotypic virulence in Salmonella was discovered in this study. The molecular mechanism concerned is described and discussed in detail in this thesis. Identification of these virulence regulatory network in Salmonella shall facilitate development of novel antimicrobial strategies based on suppression of virulence expression and survival fitness, which potentially offer a solution to the global public health problems caused by this important pathogen.