Moraxella Species

Microbiology

Discovered at the end of the 19th century, Moraxella catarrhalis (formerly Micrococcus catarrhalis , Neisseria catarrhalis, and Branhamella catarrhalis ) has undergone several changes of nomenclature and changes in status as either a commensal of the upper respiratory tract or a true pathogenic organism of both the upper and lower respiratory tract. DNA-DNA and ribosomal RNA (rRNA)–DNA hybridization techniques have shown M. catarrhalis to be more closely related to Moraxella than to Branhamella spp.

Currently, M. catarrhalis is responsible for up to 30% of cases of acute otitis media (AOM). M. catarrhalis is the second (after H. influenzae ) most common cause of exacerbations of chronic obstructive pulmonary disease in adults and is responsible for 2–4 million episodes in the US.

Members of the genus Moraxella are nonmotile, oxidase-positive, catalase-positive, aerobic, asaccharolytic, gram-negative coccobacilli or diplococci that tend to resist decolorization on Gram stain. M. catarrhalis , M. osloensis , M . nonliquefaciens, and M. lincolnii are part of the normal flora of the respiratory tract, whereas M. canis is recovered from the upper respiratory tract of cats and dogs. Colonies of M. catarrhalis grow well on both blood and chocolate agar, and some strains also grow well on modified Thayer-Martin and other selective media. Colonies are grey-white, opaque, and smooth. A useful observation for M. catarrhalis is the ability to push colonies over the surface of blood agar similar to a hockey puck on ice. M. catarrhalis is distinguished easily from Neisseria spp. by the former’s ability to hydrolyze ester-linked butyrate groups. Almost all contemporary M. catarrhalis isolates produce β-lactamase.

M. catarrhalis colonizes the mucosal surfaces of the upper and lower respiratory tracts by the expression of adhesins and activation of metabolic pathways to overcome specific nutrient limitations. Several adhesins and receptors have been identified and characterized. The family of ubiquitous surface proteins (Usps), consisting of at least 3 proteins (UspA1, UspA2, and UspA2H), consists of highly conserved and extensively studied outer membrane proteins (OMPs) with major roles in adhesion, invasion, and resistance to classic and alternative complement systems. The Moraxella immunoglobulin D (IgD)–binding protein (MID, also named hemagglutinin) is another extensively studied and highly conserved OMP that has a unique ability to bind IgD and also type II alveolar epithelial cells. ^, Interestingly, down-regulating expression of MID is associated with the persistence or colonization of M. catarrhalis in the airways of patients with chronic obstructive pulmonary disease (COPD). Fifty-seven proteins carried by outer membrane vesicles (OMVs) have been identified, including UspA1, UspA2, MID, lipo-oligosaccharide, and DNA. UspAs are the most important complement-resisting OMPs, as demonstrated in clinical isolates from patients with otitis media or COPD. ^{, ,} Strains resistant to complement-mediated killing are more virulent and adherent to epithelial cells. ^{, ,} The membrane lipo-oligosaccharides also are considered important for M. catarrhalis adhesion and virulence. ^,

M. catarrhalis can form biofilms in vitro and has been detected in biofilms in the middle ear of patients with chronic otitis media. Biofilm production by S. pneumoniae and M. catarrhalis is proposed to enhance the roles of these pathogens in recurrent AOM and otitis media with effusion. At the respiratory tract mucosal level, M. catarrhalis activates a proinflammatory response that is mainly dependent on Toll-like receptor 2 (TLR2), ^, and it also can inhibit the inflammatory cascade, thereby leading to evasion and persistent mucosal surface colonization.

Epidemiology

Colonization rates with M. catarrhalis in the upper respiratory tract vary with age, with rates highest in the first year of life (28%−100%). ^, M. catarrhalis can persist for several months, and earlier colonization in the first year is associated with higher risks of AOM and recurrent disease. Seasonal peaks of M. catarrhalis colonization and disease (winter and spring) are similar to several viral respiratory pathogens. ^, Physiologic cold shock ^, of M . catarrhalis is associated with the expression of important virulence factors, such as genes involved in adherence to epithelial cells, iron acquisition, serum resistance, and immune evasion. The risk of repeated M. catarrhalis colonization was reported to be increased in children with TLR4 Asp299Gly polymorphism. Conversely, the pili (fimbriae), cell surface organelles found on the surface of M. catarrhalis enhance pathogen clearance from the middle ear, probably mediated through neutrophil-dependent TLR5 signaling.

Five percent to 32% of older adults with COPD may have, at any time, M. catarrhalis colonizing the respiratory tract, with a median carriage duration of 30–40 days. Analysis of pediatric nasal and lung microbiomes show that increased Moraxella representation is associated with risk of asthma and risk of asthma exacerbations. Continued research is needed to determine whether this association between asthma and Moraxella reflects a specific pathogenic mechanism or if the dominance of Moraxella is a marker of decreased microbial diversity leading to increased risk of asthma. ^,

The development of mature specific IgG antibodies against M. catarrhalis is slow, and children <4 years of age have low titers of IgG antibodies. In a study analyzing the humoral immune responses to potential M. catarrhalis vaccine candidates from birth to 2 years of age, the level of antigen-specific IgG was lower than that obtained from umbilical cord blood. Young children with recurrent AOM have higher rates of nasopharyngeal colonization with M. catarrhalis and have diminished mucosal antibody response to OMP, MID, and other Moraxella surface proteins when compared to children without recurrent AOM.

Clinical Manifestations

The most frequent infections caused by M. catarrhalis are AOM, sinusitis, bronchitis, and pneumonia. Most cases of M. catarrhalis AOM resolve spontaneously. Compared with AOM caused by other pathogens, M. catarrhalis AOM is more often a mixed-infection AOM, and it is less often associated with spontaneous perforation and mastoiditis. M. catarrhalis hardly ever causes suppurative complications of AOM, such as osteomyelitis, meningitis, or brain abscess. In recent years, M. catarrhalis has become a more common etiology of AOM as cases of Streptococcus pneumoniae AOM have declined in frequency in the era of routine use of pneumococcal conjugate vaccines (PCV7, PCV13). ^,

Establishing a causative role for M. catarrhalis in children with community-acquired pneumonia is challenging because of poor diagnostic tests and frequent colonization of the upper respiratory tract. ^, M. catarrhalis bloodstream infection (BSI) is infrequently reported; it occurs in children <2 years of age, usually in association with community-acquired pneumonia, and is characterized by low-grade fever and a lack of leukocytosis but prolonged hospitalizations. M. catarrhalis can cause purulent conjunctivitis, periorbital cellulitis, endophthalmitis, keratitis, meningitis, pyogenic arthritis, pancreatitis, pericarditis, endocarditis, prosthetic vascular graft infections, pleural effusion, or localized abscesses. In immunocompromised patients, M. catarrhalis septicemia is reported in patients with leukemia, HIV, and agammaglobulinemia.

Septicemia in children due to M. osloensis, M. nonliquefaciens, and M. lacunata has been reported associated with diarrhea . Septicemia and pyogenic arthritis caused by M. nonliquefaciens have also been reported. M. osloensis has been associated with endocarditis, osteomyelitis, peritonitis, catheter-related BSI, and other deep-seated infections. Moraxella spp., including M. nonliquefaciens and M. osloensis, can cause keratitis and endophthalmitis, which often is associated with a history of ocular surgery or diabetes. ^, M. canis, an inhabitant of the upper respiratory tract of dogs and cats, has been associated rarely