The Bacteria Speaks: Understanding the Languages and Roles in Virulence

Many pathogenic bacteria produce an array of products that contribute to their virulence. In the majority of cases, expression of these virulence factors is not constitutive but strategically regulated in a cell-density dependent fashion. This phenomenon confers a pathogenic advantage on the invading bacteria such that they remain undetected by the host immune system until they have reached a critical population density to overwhelm host defenses and establish the infection. Through cell-to-cell communication, a minimal population unit or “quorum” of bacteria is achieved; hence the term “quorum sensing”. This discovery of intracellular communication among bacteria has essentially dispelled belief that only multicellular organisms are capable of coordinated activity. Individual bacterial cell is able to sense in their growth millieu the accumulation of diffusible signal molecules called autoinducers (AI) that are in turn responsible for the initiation and coordination of a variety of population responses. Quorum sensing in gram-negative bacteria involves two regulatory components: the transcriptional activator protein (R protein) and the AI molecules produced by the autoinducer synthase. Typically, gram-negative AI molecules are N-acyl-homoserine lactones (N-AHL).Upon reaching an intracellular threshold concentration, the AI binds to its cognate R protein to activate or repress specific genes. In opportunistic pathogens, these target genes are those involved in the regulation and production of a host of virulence factors including exotoxins, enzymes, biofilm production or antibiotic resistance. Melioidosis is a disease caused by the opportunistic bacteria Burkholderia pseudomallei. One of the most perplexing problems about melioidosis is its apparent ability to exist in a dormant stage and to emerge at some later time when the host’s immune response is compromised. Chronicity or prolonged latency of this disease often leads to misdiagnosis and high fatality in individuals with predisposing conditions. The exact mechanism causing recrudescence of melioidosis is presently not well understood. Quorum sensing may well provide the answer to this mystery. Investigations into the existence and genetic expression of QS phenomenon in B. pseudomallei will help unravel the puzzle surrounding recrudescent melioidosis. The role of QS in the pathogenicity of B. pseudomallei needs to be understood with respect to the regulation and expression of virulence-associated genes coding for the production of its virulence determinants including exotoxin, extracellular proteases, pili, capsules and biofilms. It is of interest also to determine if its QS molecules possess any pharmacological and immunomodulatory activity that contribute to the pathogenicity of the organism. The ability to downregulate virulence-associated gene expression through blockade of cell-to-cell communication may offer a novel strategy for preventing the recrudescence of latent infections by B. pseudomallei in immunocompromised hosts.