COMMON THEMES IN MICROBIAL PATHOGENICITY REVISITED

Bacterial pathogens employ a number of genetic strategies to cause inf ection and occasionally, disease in their hosts. Many of these virulen ce factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. The se common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a larg e number of host targets. Similarly, there are only a few conserved wa ys to build the bacterial pilus and nonpilus adhesins used by pathogen s to adhere to host substrates. Bacterial entry into host cells (invas ion) is a complex mechanism. However; several common invasion themes e xist in diverse microorganisms. Similarly, once inside a host cell, pa thogens have a limited number of ways to ensure their survival whether remaining within a host vacuole or by escaping into the cytoplasm. Av oidance of the host immune defenses is key to the success of a pathoge n. Several common themes again are employed, including antigenic varia tion camouflage by binding host molecules, and enzymatic degradation o f host immune components. Most virulence factors are found on the bact erial surface or secreted into their immediate environment, yet virule nce factors operate through a relatively small number of microbial sec retion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate rime that causes infection. Finally, virulence fac tors maintained on mobile genetic elements and pathogenicity islands e nsure that new strains of pathogens evolve constantly. Comprehension o f these common themes in microbial pathogenicity is critical to the un derstanding and study of bacterial virulence mechanisms and to the dev elopment of new ''anti-virulence'' agents, which are so desperately ne eded to replace antibiotics.