Antibiotic Susceptibilities Among Recent Clinical Isolates of Haemophilus influenzae and Moraxella catarrhalis from Fifteen Countries

Bandak, Stephen; Turnak, M.R.; Allen, Bradley S.; Bolzon, Lynda; Preston, David A.; Bouchillon, S.; Hoban, Daryl J.

doi:10.1007/pl00011235

Cited by 17 publications

(10 citation statements)

References 9 publications

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“…In the lower respiratory tract, M. catarrhalis can cause respiratory infections in adults with chronic obstructive pulmonary disease, resulting in increased morbidity and mortality of these patients (27,28). M. catarrhalis is thought to be responsible for 2 to 4 million infectious exacerbations of chronic obstructive pulmonary disease in the United States each year (25), and there is significant cost in treating disease related to M. catarrhalis, which is complicated in part by a rise in antibiotic-resistant strains (2,30). This makes development of a vaccine an exciting and important goal.…”

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Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

et al. 2007

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Moraxella catarrhalis is a human-restricted pathogen that can cause respiratory tract infections. In this study, we identified a previously uncharacterized 24-kDa outer membrane protein with a high degree of similarity to Neisseria Opa protein adhesins, with a predicted ␤-barrel structure consisting of eight antiparallel ␤-sheets with four surface-exposed loops. In striking contrast to the antigenically variable Opa proteins, the M. catarrhalis Opa-like protein (OlpA) is highly conserved and constitutively expressed, with 25 of 27 strains corresponding to a single variant. Protease treatment of intact bacteria and isolation of outer membrane vesicles confirm that the protein is surface exposed yet does not bind host cellular receptors recognized by neisserial Opa proteins. Genome-based analyses indicate that OlpA and Opa derive from a conserved family of proteins shared by a broad array of gram-negative bacteria.Moraxella catarrhalis is an obligate parasite of humans that can cause disease in both the upper and lower respiratory tracts. In the upper respiratory tract, M. catarrhalis is responsible for cases of sinusitis and is the third leading cause of otitis media in infants, after only Haemophilus influenzae and Streptococcus pneumoniae (5,10,18,24). In the lower respiratory tract, M. catarrhalis can cause respiratory infections in adults with chronic obstructive pulmonary disease, resulting in increased morbidity and mortality of these patients (27,28). M. catarrhalis is thought to be responsible for 2 to 4 million infectious exacerbations of chronic obstructive pulmonary disease in the United States each year (25), and there is significant cost in treating disease related to M. catarrhalis, which is complicated in part by a rise in antibiotic-resistant strains (2, 30). This makes development of a vaccine an exciting and important goal.The mechanisms involved in pathogenesis and virulence of M. catarrhalis remain poorly defined. Attachment to host mucosal surfaces is an important step in colonization. Recently, M. catarrhalis genes encoding the type IV pilus were identified and characterized (23), leading to speculation that this structure mediates initial attachment to mucosal epithelia in a manner similar to that of the closely related pathogenic Neisseria spp. (9). M. catarrhalis can also interact with the A549 human lung epithelial carcinoma cell line through the bacterium's outer membrane protein CD (16) and Hag (17) adhesins. Another adhesin, UspA1, promotes attachment to Chang human conjunctiva-derived epithelial cells (21) and was recently shown to mediate adherence via the host cellular receptor CEACAM1 (15). Human CEACAM1 is also engaged by the adhesins of other bacteria, including the Haemophilus influenzae P5 protein (14) and the Opa proteins of pathogenic and commensal Neisseria spp. (12,29,35). Remarkably, the UspA1, P5, and Opa proteins are not related, indicating a clear example of convergent evolution by these various human-restricted bacteria.Considering the importance of the Opa family of ...

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Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

et al. 2007

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“…Clinical and epidemiological studies revealed high carriage rates in young children and suggested that a high rate of colonization was associated with an increased risk of the development of M. catarrhalis-mediated diseases (28). In addition, the number of antibiotic-resistant strains of M. catarrhalis has increased significantly over the past decades (5,18). Currently, the molecular pathogenesis of M. catarrhalis infection is not fully understood, and there is no vaccine to prevent M. catarrhalis infections (27).…”

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Moraxella catarrhalisBacterium without Endotoxin, a Potential Vaccine Candidate

et al. 2005

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Lipooligosaccharide (LOS) is a major surface component of Moraxella catarrhalis and a possible virulence factor in the pathogenesis of human infections caused by this organism. The presence of LOS on the bacterium is an obstacle to the development of vaccines derived from whole cells or outer membrane components of the bacterium. An lpxA gene encoding UDP-N-acetylglucosamine acyltransferase responsible for the first step of lipid A biosynthesis was identified by the construction and characterization of an isogenic M. catarrhalis lpxA mutant in strain O35E. The resulting mutant was viable despite the complete loss of LOS. The mutant strain showed significantly decreased toxicity by the Limulus amebocyte lysate assay, reduced resistance to normal human serum, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. Importantly, the mutant elicited high levels of antibodies with bactericidal activity and provided protection against a challenge with the wild-type strain. These data suggest that the null LOS mutant is attenuated and may be a potential vaccine candidate against M. catarrhalis.Moraxella catarrhalis, a gram-negative diplococcus, is the third most common isolate after Streptococcus pneumoniae and nontypeable Haemophilus influenzae as the causative agent of otitis media, which is the leading cause of conductive hearing loss in children, and of the exacerbation of chronic obstructive pulmonary diseases in adults, which is the fourth leading cause of death in the United States (7,23,41). In immunocompromised hosts, M. catarrhalis causes a variety of severe infections, including septicemia and meningitis. Clinical and epidemiological studies revealed high carriage rates in young children and suggested that a high rate of colonization was associated with an increased risk of the development of M. catarrhalis-mediated diseases (28). In addition, the number of antibiotic-resistant strains of M. catarrhalis has increased significantly over the past decades (5, 18). Currently, the molecular pathogenesis of M. catarrhalis infection is not fully understood, and there is no vaccine to prevent M. catarrhalis infections (27).Active immunization with a vaccine would be an efficient approach for the prevention of M. catarrhalis infections. At present, we have only limited knowledge about which antigens confer protective immunity against M. catarrhalis infections. Whole cells or components on the surface of the bacterium, such as outer membrane proteins (OMPs), should induce specific immunity (27). A major obstacle to the development of safe and effective vaccines derived from the cells or outer membrane is the presence of toxic lipooligosaccharide (LOS). LOS is a main outer membrane component of M. catarrhalis and a potential virulence factor in the pathogenesis of infections (9, 12). Unlike the lipopolysaccharide (LPS) of enteric bacteria, M. catarrhalis LOS consists only of an oligosaccharide core and lipid A (10). In contrast to most of the LOS o...

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“…Sporadic cases of conjunctivitis, meningitis, endocarditis, ophthalmia neonatorum, keratitis, urethritis, peritonitis, and septicemia have also been reported in individuals with reduced immune defense (36). In addition, the number of antibiotic-resistant strains of M. catarrhalis has significantly increased over the past decades (3,23). Currently, the molecular pathogenesis of M. catarrhalis infection is not fully understood.…”

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Roles of 3-Deoxy- d - manno -2-Octulosonic Acid Transferase from Moraxella catarrhalis in Lipooligosaccharide Biosynthesis and Virulence

et al. 2005

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Lipooligosaccharide (LOS), a major outer membrane component of Moraxella catarrhalis, is a possible virulence factor in the pathogenesis of human infections caused by the organism. However, information about the roles of the oligosaccharide chain from LOS in bacterial infection remains limited. Here, a kdtA gene encoding 3-deoxy-D-manno-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic kdtA mutant in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any core oligosaccharide, and it was viable. Physicochemical and biological analysis revealed that the mutant was susceptible to hydrophobic reagents and a hydrophilic glycopeptide and was sensitive to bactericidal activity of normal human serum. Importantly, the mutant showed decreased toxicity by the Limulus amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data suggest that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria in vitro and in vivo. This study may bring new insights into novel vaccines or therapeutic interventions against M. catarrhalis infections.Moraxella catarrhalis, a gram-negative diplococcus, is now considered to be an important human respiratory tract pathogen in children and adults (6,29). In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss, while in adults it exacerbates chronic obstructive pulmonary diseases, the fourth leading cause of death in the United States. Sporadic cases of conjunctivitis, meningitis, endocarditis, ophthalmia neonatorum, keratitis, urethritis, peritonitis, and septicemia have also been reported in individuals with reduced immune defense (36). In addition, the number of antibiotic-resistant strains of M. catarrhalis has significantly increased over the past decades (3, 23). Currently, the molecular pathogenesis of M. catarrhalis infection is not fully understood. Based on limited information about this organism and other respiratory tract pathogens, it is generally believed that it has several virulence factors involved in colonization, adherence, or complement resistance that enable the organism to evade the normal host defense and to establish the infection (47).Previous studies suggested that complement resistance involving multifactorial processes might be an important mechanism of M. catarrhalis virulence. Several M. catarrhalis isogenic mutants of UspA2 (1, 30), Fur (15), CopB (22), and outer membrane protein (OMP) E (37) showed their susceptibility to the bactericidal activity of normal human serum when compared with their parental strains. This indicates that these bacterial components may play critical roles for the bacterial resistance to killing caused by normal human serum. In addition, ...

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Antibiotic Susceptibilities Among Recent Clinical Isolates of Haemophilus influenzae and Moraxella catarrhalis from Fifteen Countries

Cited by 17 publications

References 9 publications

Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

Moraxella catarrhalisBacterium without Endotoxin, a Potential Vaccine Candidate

Roles of 3-Deoxy- d - manno -2-Octulosonic Acid Transferase from Moraxella catarrhalis in Lipooligosaccharide Biosynthesis and Virulence

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