Expression of the Oligopeptide Permease Operon of Moraxella catarrhalis Is Regulated by Temperature and Nutrient Availability

Abstract

Moraxella catarrhalis causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Together, these two conditions contribute to enormous morbidity and mortality worldwide. The oligopeptide permease (opp) ABC transport system is a nutritional virulence factor important for the utilization of peptides. The substrate binding protein OppA, which binds peptides for uptake, is a potential vaccine antigen, but little was known about the regulation of gene expression. The five opp genes oppB, oppC, oppD, oppF, and oppA are in the same open reading frame. Sequence analysis predicted two promoters, one located upstream of oppB and one within the intergenic region between oppF and oppA. We have characterized the gene cluster as an operon with two functional promoters and show that cold shock at 26°C for <0.5 h and the presence of a peptide substrate increase gene transcript levels. Additionally, the putative promoter upstream of oppA contributes to the transcription of oppA but is not influenced by the same environmental cues as the promoter upstream of oppB. We conclude that temperature and nutrient availability contribute to the regulation of the Opp system, which is an important nutritional virulence factor in M. catarrhalis. Moraxella catarrhalis is an increasingly important human-specific pathogen contributing to worldwide morbidity and mortality that has transitioned from an emerging to an established pathogen (1-3). Otitis media in children is the primary cause of new antibiotic prescriptions and pediatric office visits, with M. catarrhalis accounting for 10% to 20% of acute otitis media episodes (2, 4-6). Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, with M. catarrhalis contributing to at least 10% of exacerbations (7-11). The socioeconomic burden of otitis media and COPD is significant, with an estimated $50 billion dollars annually in health care expenses globally (5, 9, 12). In view of the morbidity and health care cost associated with M. catarrhalis, it is important to understand the mechanisms of pathogenesis in order to guide development of novel approaches to treatment and prevention (2,13,14). In previous work, we identified OppA as a promising vaccine antigen and a nutritional virulence factor for M. catarrhalis (15,16).We previously characterized the oligopeptide permease (opp) gene cluster as an ABC transport system vital for the utilization of peptide substrates. The gene cluster encodes two permeases, OppB and OppC; two ATPases, OppD and OppF; and a substrate binding protein, OppA (16). We hypothesized that this gene cluster was transcribed as an operon and that environmental factors, temperature and essential nutrients available as peptides, would alter the rate of transcription.The lower respiratory tract has a normal body temperature of 37°C, while the upper airways, specifically the nasopharynx, where M. catarrhalis first colonizes, ranges from 34°C at room temperature (25°C) down to 26°C after a short...

Panel 8: Vaccines and immunology

“…Each antigen expresses epitopes on the bacterial surface, is conserved among strains, and induces enhanced clearance in the mouse pulmonary clearance model following immunization. In addition to the identification of new antigens, important advances have been made in developing existing M. catarrhalis vaccine antigens [68][69][70][71], Table 1.…”

Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2

“…Previously described methods were used ( 48 , 49 ). Briefly, thawed bacterial pellets were resuspended in 500 mL RNA Wiz (RiboPure RNA Purification kit for bacteria; Ambion, Life Technologies, Grand Island, NY).…”

Toxicity and inhibition mechanism of gallic acid on physiology and fermentation performance of Escherichia coli

“…In this work, genes ompF and ompC were down-regulated by 31.1 and 8.1-folds, respectively. Opp systems related to the absorption of oligopeptides are sensitive to the amount of available peptide substrate in the surrounding medium (Jones et al 2015). Genes of oppA, oppC, oppD, and oppF from Opp systems were downregulated by 3.8, 2.4, 2.5, 2.0, and 3.6-folds, respectively.…”