Haemophilus Influenzae: Virulence Factors

Haemophilus influenzae is a pleomorphic, gram-negative coccobacillus that is divided into two groups: unencapsulated (non-typeable) and encapsulated. Encapsulated strains of Haemophilus influenzae are further classified into 6 different serotypes (a-f) based on the presence of capsular polysaccharide, with the Haemophilus influenzae serotype b (Hib) being the most virulent strain.

In spite of the name, H. influenzae do not cause influenza (the flu).

Haemophilus influenzae type b (Hib) is one of the major causes of meningitis, epiglottitis, osteomyelitis, septic arthritis, pneumonia, otitis media, sinusitis, and septicaemia. in children below 5 years of age especially in those countries where vaccination coverage is limited.

Children younger than 5 years old are at highest risk of getting Hib disease and having serious complications. Getting all doses of H. influenzae type b (Hib) vaccine protects them against Hib disease.

Nontypeable strains of H. influenzae (NTHi) frequently colonize the upper respiratory tract of children and adults and can cause mucosal infections, including otitis media, conjunctivitis, sinusitis, bronchitis, and pneumonia. Both Hib and NTHi cause infections in adults but more invasive cases are reported by NTHi.

Haemophilus influenzae has several virulence factors that play a crucial role in patient inflammatory response.

Major virulence factors of H. influenzae are:

Capsule

Encapsulated H. influenzae contains capsular polysaccharides of one of six types (a-f). Capsule protects Hib from host immune functions and known plays a major role for its invasiveness.
The capsular antigen of type b is a polyribosyl ribitol phosphate (PRP). The capsule is antiphagocytic and one of the major virulence factors of H. influenzae.  PRP facilitates invasion of the bloodstream and spread of infection by the hematogenous route.

Adhesion proteins

Adhesin proteins such as HMW1 and HMW2 mediate attachment to the human epithelial cells in the airway. Adhesion proteins play major roles in the attachment of nontypeable Haemophilus influenzae (NTHi) to the respiratory epithelium which in turn promotes colonization and subsequent epithelial and endothelial invasion by this bacteria.

Lipooligosaccharides (LOS)

H. influenzae produces no exotoxins. The lipooligosaccharide is the endotoxins that plays role in the attachment and invasiveness of this organism. Paralysis of the ciliated respiratory epithelium by LOS thwart its mechanical clearance as a part of a non-specific host defense mechanism.  In NTHi stains, LOS is a critical factor for defense against host complement.

Pili

Pili and the major outer membrane P2 protein bind sialic acid-containing moieties on epithelial cell surfaces

Outer membrane proteins

They contribute in adhesion and invasion of host tissues.

IgA1 protease

H. influenzae produces IgA1protease which cleaves immunoglobulin A at the hinge region. The activity of IgA1 protease is thought to prevent agglutination at the mucosal surface and subsequent mechanical clearance of the pathogen. Increased levels of IgA protease activity correlated with increased invasiveness of NTHi strains in humans

Phase variation

Phase variation helps in immune evasion by the modification of outer surface protein of the pathogen which helps the pathogen to adapt to changes in the host environment. Hemoglobin bind proteins (HgbA, HgbB, HgBC) and adhesins (OapA, HMW1, HMW2) etc are shown to undergo phase variation.

References

1. Wayoff, M., & Jankowski, R. (1989). Virulence factors of Haemophilus influenzae. Journal of chemotherapy (Florence, Italy), 1(4 Suppl), 26–28.
2. Wispelwey, B., Hansen, E. J., Lesse, A., & Scheld, W. M. (1989). Haemophilus influenzae virulence factors in experimental meningitis. The Pediatric infectious disease journal, 8(12), 903–904. https://doi.org/10.1097/00006454-198912000-00035