Altered expression of oligopeptide-binding protein (OppA) and aminoglycoside resistance in laboratory and clinical Escherichia coli strains

Acosta, María Beatriz Riverón; Ferreira, Rita de Cássia Café; Padilla, Gabriel; Ferreira, Luís Carlos S.; Costa, Samuel Macedo

doi:10.1099/0022-1317-49-5-409

Cited by 39 publications

(40 citation statements)

References 10 publications

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“…The increase in the oppA transcript level is dramatically higher than the increase seen for the other opp genes, indicating that the promoter upstream of oppA is sensitive to the amount of available peptide substrate in the surrounding medium. Similar increases in the levels of homologous OppA proteins with the increased availability of substrates in the surrounding environment support these conclusions (40,60).…”

Section: Figsupporting

confidence: 69%

“…The regulation of this system in response to changing conditions such as cold shock and limiting essential nutrients has not been investigated. An understanding of such systems is necessary for the development of new antimicrobial agents for which ABC transporters are increasingly important targets (15,27,(39)(40)(41)(42)(43). Furthermore, as OppA was developed as a vaccine antigen, it is important to characterize the regulation of its expression.…”

Section: Discussionmentioning

confidence: 99%

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

Jones

Murphy

2015

Infect Immun

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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...

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Section: Figsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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

Jones

Murphy

2015

Infect Immun

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“…Acosta et al reported that an OppA protein purified from an E. coli K-12 strain exhibited resistance to various aminoglycoside antibiotics (1). Moreover, nine potential drug transporters belonging to resistance-nodulation-division-type systems, drug efflux systems of the major facilitator, multidrug and toxic compound extrusion systems, or ABC superfamilies in Salmonella enterica have been hypothesized to play important roles in multidrug resistance and virulence phenotypes (28).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Vibrio furnissii Oligopeptide Permease and Characterization of Its In Vitro Hemolytic Activity

Wang

Chen

et al. 2007

J Bacteriol

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We describe purification and characterization of an oligopeptide permease protein (Hly-OppA) from Vibrio furnissii that has multifaceted functions in solute binding, in in vitro hemolysis, in antibiotic resistance, and as a virulence factor in bacterial pathogenesis. The solute-binding function was revealed by N-terminal and internal peptide sequences of the purified protein and was confirmed by discernible effects on oligopeptide binding, by accumulation of fluorescent substrates, and by fluorescent substrateantibiotic competition assay experiments. The purified protein exhibited host-specific in vitro hemolytic activity against various mammalian erythrocytes and apparent cytotoxicity in CHO-K1 cells. Recombinant Hly-OppA protein and an anti-Hly-OppA monoclonal antibody exhibited and neutralized the in vitro hemolytic activity, respectively, which further confirmed the hemolytic activity of the gene product. In addition, a V. furnissii hly-oppA knockout mutant caused less mortality than the wild-type strain when it was inoculated into BALB/c mice, indicating the virulence function of this protein. Finally, the in vitro hemolytic activity was also confirmed with homologous ATP-binding cassette-type transporter proteins from other Vibrio species.

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“…Bacterial OppAs are capable of binding a wide variety of peptides and play a key role in nutrient peptide uptake and muropeptide recycling (36). OppAs are also involved in a number of other functions of bacterial physiology, including competence and sporulation (4,22,45), biofilm formation (23), adherence to host cells (12,20), growth and intracellular survival (7), modulation of the expression of virulence factors (56), and antibiotic resistance (1).…”

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confidence: 99%

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

2011

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Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.Moraxella catarrhalis is a Gram-negative diplococcus frequently found as a commensal of the upper respiratory tract (14,19). However, over the past 2 to 3 decades this bacterium has shifted from being considered a harmless commensal to being recognized as a genuine respiratory tract pathogen of serious public health concern (34, 54).Acute otitis media is the most common bacterial infection in children, with 70% experiencing at least one episode by age 3 (53). M. catarrhalis is the third leading cause of otitis media after Streptococcus pneumoniae and nontypeable Haemophilus influenzae (21,34). M. catarrhalis is associated with up to 25% of acute otitis media cases by culture (37) and 46.4% of chronic middle ear effusion cases by PCR (41). In addition, the nasopharyngeal carriage rate of M. catarrhalis in children is high (up to 75%) and the frequency of colonization is positively related to the development of otitis media (14).In adults, M. catarrhalis is the second most common bacterial cause of exacerbations of chronic obstructive pulmonary disease (COPD) after nontypeable H. influenzae (33,48,49). COPD is the fourth leading cause of death in the United States, affecting 24 million Americans (25, 26). M. catarrhalis causes approximately 10% of exacerbations of COPD, accounting for 2 to 4 million episodes annually (33). Furthermore, M. catarrhalis also colonizes the lower respiratory tract in up to 2.5 to 10% of adults with COPD at their stable states (31, 59). Lower airway colonization contributes to airway inflammation in COPD as a result of sloughing of highly inflammatory bacterial cell wall antigens into the airway (49).The significant clinical implications of M. catarrhalis require a vaccine targeting bo...

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Altered expression of oligopeptide-binding protein (OppA) and aminoglycoside resistance in laboratory and clinical Escherichia coli strains

Cited by 39 publications

References 10 publications

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

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

Identification of a Vibrio furnissii Oligopeptide Permease and Characterization of Its In Vitro Hemolytic Activity

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

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