Journal Article

ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence

Murphy, Timothy F, Johnson, Antoinette, Kirkham, Charmaine, Brauer, Aimee L.

2016

Overview

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: A549 Cells / ABC transporter / ABC transporters / Adults / Amino acids / Analysis / Animals / Anions / Antigens / Antimicrobial agents / ATP / ATP-Binding Cassette Transporters - genetics / ATP-Binding Cassette Transporters - metabolism / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Binding / Biology and Life Sciences / Cations / Chemical properties / Children / Chronic obstructive pulmonary disease / Ear diseases / Epithelial cells / Epithelial Cells - metabolism / Epithelial Cells - microbiology / Genetic aspects / Genome, Bacterial - genetics / Genomes / Health aspects / Humans / Immunization / Infections / Infectious diseases / Influence / Lung diseases / Lungs / Medicine / Medicine and Health Sciences / Mice, Inbred BALB C / Microenvironments / Middle ear / Moraxella (Branhamella) catarrhalis - metabolism / Moraxella (Branhamella) catarrhalis - pathogenicity / Moraxella catarrhalis / Mutants / Native peoples / Nutrients / Obstructive lung disease / Otitis media / Pathogenesis / Pathogens / Peptides / Protein binding / Proteins / Respiratory System - metabolism / Respiratory System - microbiology / Respiratory tract / Respiratory tract diseases / Respiratory Tract Infections - genetics / Respiratory Tract Infections - metabolism / Substrates / Vaccines / Virulence / Virulence (Microbiology) / Virulence factors