X. Frank Yang

School of Medicine, Microbiology & Immunology

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Abrogation of ospAB constitutively activates the Rrp2-RpoN-RpoS pathway (sigmaN-sigmaS cascade) in Borrelia burgdorferi

Ming He; Tara Oman; Haijun Xu; Jon Blevins; Michael V. Norgard; X. Frank Yang (Profiled Author: X. Frank Yang)

Molecular Microbiology. 2008;70(6):1453-1464.

Molecular mechanisms underlying the reciprocal regulation of the two major surface lipoproteins and virulence factors of Borrelia burgdorferi, OspA and OspC, are not fully understood. Herein, we report that inactivation of the ospAB operon resulted in overproduction of OspC and many other lipoproteins via the constitutive activation of the Rrp2-RpoN-RpoS pathway. Complementing the ospAB mutant with a wild-type copy of ospA, but not an ospA variant that lacks the lipoprotein signal sequence, restored normal regulation of the Rrp2-RpoN-RpoS pathway; these results indicate that the phenotype was not caused by spurious mutations. Interestingly, while most of the ospAB mutant clones displayed a constitutive ospC expression phenotype, some ospAB mutant clones showed little or no ospC expression. Further analyses revealed that this OspC-negative phenotype was independent of abrogation of ospAB. While activation of the Rrp2-RpoN-RpoS pathway was recently shown to downregulate ospA, our findings suggest that reduction of OspA can also activate this pathway. We postulate that the activation of the Rrp2-RpoN-RpoS pathway and downregulation of OspA form a positive feedback loop that allows spirochaetes to produce and maintain a constant high level of OspC and other lipoproteins during tick feeding, a strategy that is critical for spirochaetal transmission and mammalian infection. © 2008 The Authors.

PMID: 19019147     PMCID: PMC2792205

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