Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 142 No. 4344 (2012)

Molecular pathogenesis of infections caused by Moraxella catarrhalis in children

  • Sara Bernhard
  • Violeta Spaniol
  • Christoph Aebi
Cite this as:
Swiss Med Wkly. 2012;142:w13694


Moraxella catarrhalis (M. catarrhalis) is a human-restricted commensal of the normal bacterial flora in the upper respiratory tract of children, and – during the previous two decades – has been recognised as a true human pathogen. M. catarrhalis is the third most common pathogen causing acute otitis media in children, which is the most common reason to visit a paediatrician during childhood. Acute otitis media thus causes a high clinical and economical burden. With the introduction of the conjugate pneumococcal vaccines the microbiomic pattern in the nasopharyngeal flora of children has changed, and the frequency of isolation of M. catarrhalis has increased. Compared to adults, children are more often colonised with M. catarrhalis.

Over the last three decades there has been a dramatic increase in the acquisition of β-lactam resistance in M. catarrhalis. Today 95–100% of clinically isolated M. catarrhalis produce β-lactamase. It is thus desirable to reduce the burden of M. catarrhalis disease by developing a vaccine. There are several potential vaccine antigen candidates in different stages of development, but none of them has entered clinical trials at the present time.


  1. Frosch P, Kolle W. Die Mikrokokken. Die Mikroorganismen. Leipzig: Verlag von Vogel; 1896. p. 154–5.
  2. Berger U. Die anspruchslosen Neisserien. Exp Ther. 1963;(35):97–167.
  3. Catlin B. Transfer ot the organsim named Neisseria catarrhalis to Branhamella gen. nov. Int J Syst Bacteriol. 1970;20(2):155–9.
  4. Bovre K. The genus Moraxella Bergy’s Manual of Systematic Bacteriology. Baltimore: The Williams & Wilkens Co; 1984.
  5. Bootsma HJ, van der Heide HG, van de Pas S, Schouls LM, Mooi FR. Analysis of Moraxella catarrhalis by DNA typing: evidence for a distinct subpopulation associated with virulence traits. J Infect Dis. 2000;181(4):1376–87.
  6. Wirth T, Morelli G, Kusecek B, van Belkum A, van der Schee C, Meyer A, et al. The rise and spread of a new pathogen: seroresistant Moraxella catarrhalis. Genome Res. 2007;17(11):1647–56.
  7. Meier PS, Troller R, Heiniger N, Hays JP, van Belkum A, Aebi C. Unveiling electrotransformation of Moraxella catarrhalis as a process of natural transformation. FEMS Microbiol Lett. 2006;262(1):72–6.
  8. Sano N, Matsunaga S, Akiyama T, Nakashima Y, Kusaba K, Nagasawa Z, et al. Moraxella catarrhalis bacteraemia associated with prosthetic vascular graft infection. J Med Microbiol. 2010;59(Pt 2):245–50.
  9. Post JC, White GJ, Aul JJ, Zavoral T, Wadowsky RM, Zhang Y, et al. Development and validation of a multiplex PCR-based assay for the upper respiratory tract bacterial pathogens haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Mol Diagn. 1996;1(1):29–39.
  10. Faden H, Harabuchi Y, Hong JJ, Epidemiology of Moraxella catarrhalis in children during the first 2 years of life: relationship to otitis media. J Infect Dis. 1994;169(6):1312–7.
  11. Verhaegh SJ, Lebon A, Saarloos JA, Verbrugh HA, Jaddoe VW, Hofman A, et al. Determinants of Moraxella catarrhalis colonization in healthy Dutch children during the first 14 months of life. Clin Microbiol Infect. 2010;16(7):992–7.
  12. Verhaegh SJ, Snippe ML, Levy F, Verbrugh HA, Jaddoe VW, Hofman A, et al. Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae. Microbiology. 2011;157(Pt 1):169–78.
  13. Vaneechoutte M, Verschraegen G, Claeys G, Weise B, Van den Abeele AM. Respiratory tract carrier rates of Moraxella (Branhamella) catarrhalis in adults and children and interpretation of the isolation of M. catarrhalis from sputum. J Clin Microbiol. 1990;28(12):2674–80.
  14. Ejlertsen T, Thisted E, Ebbesen F, Olesen B, Renneberg J. Branhamella catarrhalis in children and adults. A study of prevalence, time of colonisation, and association with upper and lower respiratory tract infections. J Infect. 1994;29(1):23–31.
  15. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y, Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics. J Infect Dis. 1997;175(6):1440–5.
  16. Cook PP, Hecht DW, Snydman DR. Nosocomial Branhamella catarrhalis in a paediatric intensive care unit: risk factors for disease. J Hosp Infect. 1989;13(3):299–307.
  17. Levy F, Leman SC, Sarubbi FA, Walker ES. Nosocomial transmission clusters and risk factors in Moraxella catarrhalis. Epidemiol Infect. 2009;137(4):581–90.
  18. Wood GM, Johnson BC, McCormack JG. Moraxella catarrhalis: pathogenic significance in respiratory tract infections treated by community practitioners. Clin Infect Dis. 1996;22(4):632–6.
  19. Sarubbi FA, Myers JW, Williams JJ, Shell CG. Respiratory infections caused by Branhamella catarrhalis. Selected epidemiologic features. Am J Med. 1990;88(5A):9S–14S.
  20. Duppenthaler A, Gorgievski-Hrisoho M, Frey U, Aebi C. Two-year periodicity of respiratory syncytial virus epidemics in Switzerland. Infection. 2003;31(2):75–80.
  21. Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. J Clin Microbiol. 2011;49(11):3750–5.
  22. Heiniger N, Troller R, Meier PS, Aebi C. Cold shock response of the UspA1 outer membrane adhesin of Moraxella catarrhalis. Infect Immun. 2005;73(12):p. 8247–55.
  23. Spaniol V, Troller R, Schaller A, Aebi C. Physiologic cold shock of Moraxella catarrhalis affects the expression of genes involved in the iron acquisition, serum resistance and immune evasion. BMC Microbiol. 2011;11:182.
  24. Spaniol V, Troller R, Aebi C. Physiologic cold shock increases adherence of Moraxella catarrhalis to and secretion of interleukin 8 in human upper respiratory tract epithelial cells. J Infect Dis. 2009;200(10):1593–601.
  25. Stutzmann Meier P, Heiniger N, Troller R, Aebi C, Salivary antibodies directed against outer membrane proteins of Moraxella catarrhalis in healthy adults. Infect Immun. 2003;71(12):6793–8.
  26. Faden H, Hong J, Murphy T. Immune response to outer membrane antigens of Moraxella catarrhalis in children with otitis media. Infect Immun. 1992;60(9):3824–9.
  27. Bakri F, Brauer AL, Sethi S, Murphy TF. Systemic and mucosal antibody response to Moraxella catarrhalis after exacerbations of chronic obstructive pulmonary disease. J Infect Dis. 2002;185(5):632–40.
  28. Goldblatt D, Turner MW, Levinsky RJ. Branhamella catarrhalis: antigenic determinants and the development of the IgG subclass response in childhood. J Infect Dis. 1990;162(5):1128–35.
  29. Revai K, McCormick DP, Patel J, Grady JJ, Saeed K, Chonmaitree T. Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media. Pediatrics. 2006;117(5):1823–9.
  30. Broides A, Dagan R, Greenberg D, Givon-Lavi N, Leibovitz E. Acute otitis media caused by Moraxella catarrhalis: epidemiologic and clinical characteristics. Clin Infect Dis. 2009;49(11):1641–7.
  31. Rodriguez WJ, Schwartz RH. Streptococcus pneumoniae causes otitis media with higher fever and more redness of tympanic membranes than Haemophilus influenzae or Moraxella catarrhalis. Pediatr Infect Dis J. 1999;18(10):942–4.
  32. Bluestone CD. Pathogenesis of otitis media: role of eustachian tube. Pediatr Infect Dis J. 1996;15(4):281–91.
  33. Alho OP, Koivu M, Sorri M. What is an “otitis-prone” child? Int J Pediatr Otorhinolaryngol. 1991;21(3):201–9.
  34. Teele DW. Long term sequelae of otitis media: fact or fantasy? Pediatr Infect Dis J. 1994;13(11):1069–73.
  35. Post JC, Preston RA, Aul JJ, Larkins-Pettigrew M, Rydquist-White J, Anderson KW, et al. Molecular analysis of bacterial pathogens in otitis media with effusion. JAMA. 1995;273(20):1598–604.
  36. Wald ER. Sinusitis in children. N Engl J Med. 1992;326(5):319–23.
  37. Brook I, Foote PA, Hausfeld JN. Frequency of recovery of pathogens causing acute maxillary sinusitis in adults before and after introduction of vaccination of children with the 7-valent pneumococcal vaccine. J Med Microbiol. 2006;55(Pt 7):943–6.
  38. Eliasson I, Kamme C, Vang M, Waley SG. Characterization of cell-bound papain-soluble beta-lactamases in BRO-1 and BRO-2 producing strains of Moraxella (Branhamella) catarrhalis and Moraxella nonliquefaciens. Eur J Clin Microbiol Infect Dis. 1992;11(4):313–21.
  39. Bootsma HJ, van Dijk H, Vauterin P, Verhoef J, Mooi FR. Genesis of BRO beta-lactamase-producing Moraxella catarrhalis: evidence for transformation-mediated horizontal transfer. Mol Microbiol. 2000;36(1):93–104.
  40. Schmitz FJ, Beeck A, Perdikouli M, Boos M, Mayer S, Scheuring S, et al. Production of BRO beta-lactamases and resistance to complement in European Moraxella catarrhalis isolates. J Clin Microbiol. 2002;40(4):1546–8.
  41. Hsu SF, Lin YT, Chen TL, Siu LK, Hsueh PR, Huang ST, et al. Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan. J Microbiol Immunol Infect, 2011. 2011 Dec 8. [Epub ahead of print].
  42. Gupta N, Arora S, Kundra S. Moraxella catarrhalis as a respiratory pathogen. Indian J Pathol Microbiol. 2011;54(4):769–71.
  43. Melo-Cristino J, Santos L, Silva-Costa C, Friaes A, Pinho MD, Ramirez M. The Viriato study: update on antimicrobial resistance of microbial pathogens responsible for community-acquired respiratory tract infections in Portugal. Paediatr Drugs. 2010;12(Suppl 1):11–7.
  44. Karpanoja P, Nyberg ST, Bergman M, Voipio T, Paakkari P, Huovinen P, et al. Connection between trimethoprim-sulfamethoxazole use and resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antimicrob Agents Chemother. 2008;52(7):2480–5.
  45. PIGS. Pediatric Infectious Disease Group of Switzerland, Empfehlungen zur Diagnose und Behandlung von Otitis media, Sinusitis, Pharyngitis und Pneumonie. Accessed April 4th 2012; Available from:
  46. Courter JD, Baker WL, Nowak KS, Smogowicz LA, Desjardins LL, Coleman CI, et al. Increased clinical failures when treating acute otitis media with macrolides: a meta-analysis. Ann Pharmacother. 2010;44(3):471–8.
  47. Aebi C. Moraxella catarrhalis – pathogen or commensal? Adv Exp Med Biol. 697:107–16.
  48. de Vries SP, Bootsma HJ, Hays JP, Hermans PW. Molecular aspects of Moraxella catarrhalis pathogenesis. Microbiol Mol Biol Rev. 2009;73(3):389–406, Table of Contents.
  49. Murphy TF, Parameswaran GI. Moraxella catarrhalis, a human respiratory tract pathogen. Clin Infect Dis. 2009;49(1):124–31.
  50. Bullard B, Lipski SL, Lafontaine ER. Hag directly mediates the adherence of Moraxella catarrhalis to human middle ear cells. Infect Immun. 2005;73(8):5127–36.
  51. Meier PS, Freiburghaus S, Martin A, Heiniger N, Troller R, Aebi C. Mucosal immune response to specific outer membrane proteins of Moraxella catarrhalis in young children. Pediatr Infect Dis J. 2003;22(3):256–62.
  52. Timpe JM, Holm MM, Vanlerberg SL, Basrur V, Lafontaine ER. Identification of a Moraxella catarrhalis outer membrane protein exhibiting both adhesin and lipolytic activities. Infect Immun. 2003;71(8):4341–50.
  53. Peng D, Hong W, Choudhury BP, Carlson RW, Gu XX. Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate. Infect Immun. 2005;73(11):7569–77.
  54. Hoiczyk E, Roggenkamp A, Reichenbecher M, Lupas A, Heesemann J. Structure and sequence analysis of Yersinia YadA and Moraxella UspAs reveal a novel class of adhesins. EMBO J. 2000;19(22):5989–99.
  55. Koretke KK, Szczesny P, Gruber M, Lupas AN. Model structure of the prototypical non-fimbrial adhesin YadA of Yersinia enterocolitica. J Struct Biol. 2006;155(2):154–61.
  56. Ackermann N, Tiller M, Anding G, Roggenkamp A, Heesemann J. Contribution of trimeric autotransporter C-terminal domains of oligomeric coiled-coil adhesin (Oca) family members YadA, UspA1, EibA, and Hia to translocation of the YadA passenger domain and virulence of Yersinia enterocolitica. J Bacteriol. 2008;190(14):5031–43.
  57. Brooks MJ, Sedillo JL, Wagner N, Laurence CA, Wang W, Attia AS, et al. Modular arrangement of allelic variants explains the divergence in Moraxella catarrhalis UspA protein function. Infect Immun. 2008;76(11):5330–40.
  58. Aebi C, Lafontaine ER, Cope LD, Latimer JL, Lumbley SL, McCracken GH, Jr, et al. Phenotypic effect of isogenic uspA1 and uspA2 mutations on Moraxella catarrhalis 035E. Infect Immun. 1998;66(7):3113–9.
  59. Meier PS, Troller R, Heiniger N, Grivea IN, Syrogiannopoulos GA, Aebi C. Moraxella catarrhalis strains with reduced expression of the UspA outer membrane proteins belong to a distinct subpopulation. Vaccine. 2005;23(16) 2000–8.
  60. Hill DJ, Edwards AM, Rowe HA, Virji M. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding recombinant polypeptide confers protection against infection by respiratory and urogenital pathogens. Mol Microbiol. 2005;55(5):1515–27.
  61. Tan TT, Forsgren A, Riesbeck K. The respiratory pathogen moraxella catarrhalis binds to laminin via ubiquitous surface proteins A1 and A2. J Infect Dis. 2006;194(4):493–7.
  62. Tan TT, Nordstrom T, Forsgren A, Riesbeck K. The respiratory pathogen Moraxella catarrhalis adheres to epithelial cells by interacting with fibronectin through ubiquitous surface proteins A1 and A2. J Infect Dis. 2005;192(6):1029–38.
  63. Lafontaine ER, Wagner NJ, Hansen EJ. Expression of the Moraxella catarrhalis UspA1 protein undergoes phase variation and is regulated at the transcriptional level. J Bacteriol. 2001;183(5):1540–51.
  64. Forsgren A, Brant M, Karamehmedovic M, Riesbeck K. The immunoglobulin D-binding protein MID from Moraxella catarrhalis is also an adhesin. Infect Immun. 2003;71(6):3302–9.
  65. Mollenkvist A, Nordstrom T, Hallden C, Christensen JJ, Forsgren A, Riesbeck K. The Moraxella catarrhalis immunoglobulin D-binding protein MID has conserved sequences and is regulated by a mechanism corresponding to phase variation. J Bacteriol. 2003;185(7):2285–95.
  66. Peng D, Hu WG, Choudhury BP, Muszynski A, Carlson RW, Gu XX. Role of different moieties from the lipooligosaccharide molecule in biological activities of the Moraxella catarrhalis outer membrane. FEBS J. 2007;274(20):5350–9.
  67. Verhaegh SJ, Streefland A, Dewnarain JK, Farrell DJ, van Belkum A, Hays JP. Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001–2002. Microbiology. 2008;154(Pt 4):1178–84.
  68. Spaniol V, Heiniger N, Troller R, Aebi C. Outer membrane protein UspA1 and lipooligosaccharide are involved in invasion of human epithelial cells by Moraxella catarrhalis. Microbes Infect. 2008;10(1):3–11.
  69. Slevogt H, Seybold J, Tiwari KN, Hocke AC, Jonatat C, Dietel S, et al. Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2- and partly NOD1-dependent inflammatory immune response. Cell Microbiol. 2007;9(3):694–707.
  70. Heiniger N, Spaniol V, Troller R, Vischer M, Aebi C. A reservoir of Moraxella catarrhalis in human pharyngeal lymphoid tissue. J Infect Dis. 2007;196(7):1080–7.
  71. Hall-Stoodley L, Hu FZ, Gieseke A, Nistico L, Nguyen D, Hayes J, et al. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA. 2006;296(2):202–11.
  72. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol. 2009;11(7):1034–43.
  73. Pearson MM, Laurence CA, Guinn SE, Hansen EJ. Biofilm formation by Moraxella catarrhalis in vitro: roles of the UspA1 adhesin and the Hag hemagglutinin. Infect Immun. 2006;74(3):1588–96.
  74. Murphy S, Fitzgerald M, Mulcahy R, Keane C, Coakley D, Scott T. Studies on haemagglutination and serum resistance status of strains of Moraxella catarrhalis isolated from the elderly. Gerontology. 1997;43(5):277–82.
  75. Nordstrom T, Blom AM, Forsgren A, Riesbeck K. The emerging pathogen Moraxella catarrhalis interacts with complement inhibitor C4b binding protein through ubiquitous surface proteins A1 and A2. J Immunol. 2004;173(7):4598–606.
  76. Singh B, Blom AM, Unal C, Nilson B, Morgelin M, Riesbeck K. Vitronectin binds to the head region of Moraxella catarrhalis ubiquitous surface protein A2 and confers complement-inhibitory activity. Mol Microbiol. 2010;75(6):1426–44.
  77. Attia AS, Ram S, Rice PA, Hansen EJ. Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade. Infect Immun. 2006;74(3):1597–611.
  78. Tan TT, Morgelin M, Forsgren A, Riesbeck K. Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles. J Infect Dis. 2007;195(11):1661–70.
  79. Tan TT, Riesbeck K. Current progress of adhesins as vaccine candidates for Moraxella catarrhalis. Expert Rev Vaccines. 2007;6(6):949–56.
  80. Mawas F, Ho MM, Corbel MJ. Current progress with Moraxella catarrhalis antigens as vaccine candidates. Expert Rev Vaccines. 2009;8(1):77–90.

Most read articles by the same author(s)