Complexity of Complement Resistance Factors Expressed by Needed for Survival in Human Serum.

is a bacterial pathogen with increasing impact in healthcare settings, due in part to this organism's resistance to many antimicrobial agents, with pneumonia and bacteremia as the most common manifestations of disease. A significant proportion of clinically relevant strains are resistant to killing by normal human serum (NHS), an observation supported in this study by showing that 12 out of 15 genetically diverse strains of are resistant to NHS killing. To expand our understanding of the genetic basis of serum resistance, a transposon (Tn) sequencing (Tn-seq) approach was used to identify genes contributing to this trait. An ordered Tn library in strain AB5075 with insertions in every nonessential gene was subjected to selection in NHS. We identified 50 genes essential for the survival of in NHS, including already known serum resistance factors, and many novel genes not previously associated with serum resistance. This latter group included the maintenance of lipid asymmetry genetic pathway as a key determinant in protecting from the bactericidal activity of NHS via the alternative complement pathway. Follow-up studies validated the role of eight additional genes identified by Tn-seq in resistance to killing by NHS but not by normal mouse serum, highlighting the human species specificity of serum resistance. The identification of a large number of genes essential for serum resistance in indicates the degree of complexity needed for this phenotype, which might reflect a general pattern that pathogens rely on to cause serious infections.