Abstract
ABSTRACTThe ability of bacterial pathogens to acquire essential micronutrients is critical for their survival in the host environment. Manganese plays a complex role in the virulence of a variety of pathogens due to its function as an antioxidant and enzymatic cofactor. Therefore, host cells deprive pathogens of manganese to prevent or attenuate infection. Here, we show that evolution of the human-restricted pathogen Bordetella pertussis has selected for an inhibitory duplication within a manganese exporter of the calcium:cation antiporter superfamily. Intriguingly, upon exposure to toxic levels of manganese, the nonfunctional exporter becomes operative in resister cells due to a unique reverse adaptation mechanism. However, compared with wild-type (wt) cells, the resisters carrying a functional copy of the exporter displayed strongly reduced intracellular levels of manganese and impaired growth under oxidative stress. Apparently, inactivation of the manganese exporter and the resulting accumulation of manganese in the cytosol benefited the pathogen by improving its survival under stress conditions. The inhibitory duplication within the exporter gene is highly conserved among B. pertussis strains, absent from all other Bordetella species and from a vast majority of organisms across all kingdoms of life. Therefore, we conclude that inactivation of the exporter gene represents an exceptional example of a flexible genome decay strategy employed by a human pathogen to adapt to its exclusive host.
Highlights
IMPORTANCE Bordetella pertussis, a respiratory pathogen restricted to humans, continuously adapts its genome to its exclusive host
One of the riboswitches was identified in the 59-untranslated region (UTR) of the BP3410 gene, which was annotated as a calcium:cation antiporter (Fig. 1A)
Our primary transcriptome analysis showed that the BP3410 gene is transcribed exclusively from a single promoter upstream of the riboswitch and that this transcript originates from the negative strand as the A residue at position 3,619,424 (TSS43920 in Fig. 1A) within the B. pertussis genome [37, 40]
Summary
IMPORTANCE Bordetella pertussis, a respiratory pathogen restricted to humans, continuously adapts its genome to its exclusive host. Our data demonstrate that inactivation of the exporter resulting in manganese accumulation assists B. pertussis in adaptation to oxidative stress. Mn exporters have been discovered recently in several pathogenic bacteria, and mutants lacking these exporters displayed attenuated virulence and reduced ability to survive within the host environments [16,17,18,19]. It remains to be clarified whether these effects resulted from Mn intoxication. An Mn-responsive riboswitch was shown to control expression of an Mn exporter in Escherichia coli [33] and Lactococcus lactis [34]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call