Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi

Herein, we examined the expression of rpoS and key lipoprotein genes regulated by RpoS, including ospC, ospA, and dbpA, throughout the entire tick-mammal infectious cycle of B. burgdorferi. Our data revealed that transcription of rpoS, ospC, and dbpA is highly induced in nymphal ticks when taking a blood meal. The RpoN-RpoS pathway remains active during the mammalian infection phase, as indicated by the sustained transcription of rpoS and dbpA in B. burgdorferi within mouse tissues following borrelial dissemination. However, dbpA transcription levels in fed larvae and intermolt larvae suggested that an additional layer of control likely is involved in the expression of the dbpBA operon. Our results also provide further evidence for the downregulation of ospA expression during mammalian infection, and the repression of ospC at later phases of mammalian infection by B. burgdorferi.Our study demonstrates that the RpoN-RpoS regulatory pathway is initially activated during the tick transmission of B. burgdorferi to its mammalian host, and is sustained during mammalian infection.Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi, remains the most common vector-borne disease in the United States [1]. B. burgdorferi is transmitted either to its natural mammalian host(s) or inadvertently to humans through the bite of an infected Ixodes tick vector [2,3]. In humans, B. burgdorferi causes a localized skin lesion (erythema migrans) at the initial site of infection, followed by hematogenous dissemination of the bacterium to distant sites such as the heart, joints, and central nervous system, causing carditis, arthritis, and neurological manifestations [1-3].To maintain itself in its complex tick-mammalian infectious life cycle, B. burgdorferi must adapt to two markedly different host milieus (ticks and mammals). This host adaptation is achieved, at least in part, by altering a number of its outer surface lipoproteins, which is perhaps best exemplified by