Journal Article

Cytochrome oxidase requirements in Bordetella reveal insights into evolution towards life in the mammalian respiratory tract

Mote, Katlyn B., Dedloff, Margaret R., Nash, Zachary M., Johnson, Richard M., Sobran, M. Ashley, Julio, Steven M., Marlatt, Sara A., Cotter, Peggy A., Spandrio, Alexa R., McKay, Liliana S.

2024

Overview

Little is known about oxygen utilization during infection by bacterial respiratory pathogens. The classical Bordetella species, including B . pertussis , the causal agent of human whooping cough, and B . bronchiseptica , which infects nearly all mammals, are obligate aerobes that use only oxygen as the terminal electron acceptor for electron transport-coupled oxidative phosphorylation. B . bronchiseptica , which occupies many niches, has eight distinct cytochrome oxidase-encoding loci, while B . pertussis , which evolved from a B . bronchiseptica -like ancestor but now survives exclusively in and between human respiratory tracts, has only three functional cytochrome oxidase-encoding loci: cydAB1 , ctaCDFGE1 , and cyoABCD1 . To test the hypothesis that the three cytochrome oxidases encoded within the B . pertussis genome represent the minimum number and class of cytochrome oxidase required for respiratory infection, we compared B . bronchiseptica strains lacking one or more of the eight possible cytochrome oxidases in vitro and in vivo . No individual cytochrome oxidase was required for growth in ambient air, and all three of the cytochrome oxidases conserved in B . pertussis were sufficient for growth in ambient air and low oxygen. Using a high-dose, large-volume persistence model and a low-dose, small-volume establishment of infection model, we found that B . bronchiseptica producing only the three B . pertussis -conserved cytochrome oxidases was indistinguishable from the wild-type strain for infection. We also determined that CyoABCD1 is sufficient to cause the same level of bacterial burden in mice as the wild-type strain and is thus the primary cytochrome oxidase required for murine infection, and that CydAB1 and CtaCDFGE1 fulfill auxiliary roles or are important for aspects of infection we have not assessed, such as transmission. Our results shed light on the environment at the surface of the ciliated epithelium, respiration requirements for bacteria that colonize the respiratory tract, and the evolution of virulence in bacterial pathogens.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aerobes / Animals / Bacteria / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Biological Evolution / Biology and Life Sciences / Bordetella / Bordetella - enzymology / Bordetella - genetics / Bordetella bronchiseptica - enzymology / Bordetella bronchiseptica - genetics / Bordetella bronchiseptica - metabolism / Bordetella Infections - microbiology / Bordetella pertussis - enzymology / Bordetella pertussis - genetics / Cytochrome / Cytochrome oxidase / Cytochromes / Development and progression / Electron transport / Electron Transport Complex IV - genetics / Electron Transport Complex IV - metabolism / Epithelium / Evolution / Gene loci / Genetic engineering / Genomes / Gram-negative bacterial infections / Health aspects / Humans / In vitro methods and tests / In vivo methods and tests / Infections / Mammals / Medicine and Health Sciences / Mice / Microbiological research / Oxidase / Oxidative phosphorylation / Oxygen / Pathogens / Pertussis / Phosphorylation / Physical Sciences / Physiological aspects / Proteins / Respiration / Respiratory diseases / Respiratory System - metabolism / Respiratory System - microbiology / Respiratory tract / Respiratory tract diseases / Respiratory tract infection / Respiratory Tract Infections - microbiology / Virulence / Virulence (Microbiology) / Whooping cough