Virulence factors of gram-negative bacteria in sepsis with a focus on Neisseria meningitidis

Abstract

Gram-negative bacterial pathogens of humans have evolved a range of virulence factors to promote motility, attach to epithelial or endothelial cell surfaces, avoid host immune responses, activate or inactivate host cellular pathways and ultimately cause clinical disease. Gram-negative sepsis is a life-threatening complication of these events. This review discusses the virulence factors of common Gram-negative bacteria causing human sepsis with a focus on Neisseria meningitidis. Adherence, motility, colonization and cell entry involve bacterial pili, flagella and outer membrane proteins. Endotoxin (lipopoly-or lipo-oligosaccharide), other membrane components or exotoxins can be potent inducers of the host inflammatory cascade via innate receptor pathways. Capsular polysaccharides and outer membrane proteins can help the bacterium evade immune defenses. The role in pathogenesis of iron acquisition, bacterial secretion systems, quorum sensing, and biofilm formation is also reviewed. Through multiple genetic mechanisms leading to phase variation, Gram-negative bacteria can adapt to changing host and environmental conditions and selective pressures. Further, the antimicrobial resistance of Gram-negative bacteria driven by antibiotic use will continue to influence the clinical outcomes of Gram-negative sepsis in the coming years.