[16] A minority of non-typeable, or unencapsulated, H. influenzae employ a variety of attachment techniques, such as pili, adhesins, or Hia and Hap proteins.

[21] Some antibiotic-resistant isolates of H. Influenzae contain modified PBPs that resist beta-lactam action by producing beta-lactamases to degrade these antibiotics.

[22] H. influenzae isolates were initially characterized as either encapsulated (having an extracellular polysaccharide layer, the bacterial capsule) or unencapsulated.

[25] Unencapsulated strains are termed nontypable (NTHi) because they lack capsular serotypes; however, all H. influenzae isolates can now be classified by multilocus sequence typing and other molecular methods.

Most NTHi strains are considered to be part of the normal human flora in the upper and lower respiratory tract, genitals, and conjunctivae (mucous membranes of the eye).

Haemophilus was chosen because one of the project leaders, Nobel laureate Hamilton Smith, had been working on it for decades and was able to provide high-quality DNA libraries.

In fact, the similarity between genes of the two species ranges from 18% to 98% protein sequence identity, with the majority sharing 40–80% of their amino acids (with an average of 59%).

[28] Conjugative plasmids (DNA molecules that are capable of horizontal transfer between different species of bacteria) can frequently be found in H. influenzae.

[29] H. influenzae mutants defective in their rec1 gene (a homolog of recA) are very susceptible to being killed by the oxidizing agent hydrogen peroxide.

Thus, H. influenzae may protect its genome against the reactive oxygen species produced by the host's phagocytic cells through recombinational repair of oxidative DNA damages.

Transformation in H. influenzae involves at least 15 gene products,[10] and is likely an adaptation for repairing DNA damage in the resident chromosome.

[36] Clinical diagnosis of invasive H. influenzae infection (infection that has spread to the bloodstream and internal tissues) is typically confirmed by bacterial culture, latex particle agglutination tests, or polymerase chain reaction tests on clinical samples obtained from an otherwise sterile body site.

Use of antibiotics prior to sample collection greatly reduces the isolation rate by killing the bacteria before identification is possible.

[38] Recent work has shown that H. influenzae uses a highly specialized spectrum of nutrients where lactate is a preferred carbon source.

[41] Polymerase chain reaction (PCR) assays have been proven to be more sensitive than either LAT or culture tests and are highly specific.

Colonization occurs when a microorganism continues to multiply within the host, without interaction, causing no visible signs of illness or infection.

[46] The pathogenesis of H. influenzae infections is not completely understood, although the presence of the polyribosyl ribitol phosphate (PRP) capsule in encapsulated type b (Hib), a serotype causing conditions such as epiglottitis, is known to be a major factor in virulence.

In healthy children under the age of 5, H. influenzae type b was responsible for more than 80% of aggressive infections, before the introduction of the [Hib] vaccine.

[50] In infants and young children, H. influenzae type b (Hib) causes bacteremia, pneumonia, epiglottitis and acute bacterial meningitis.

[51] However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where the vaccine is not widely used.

[51] Some strains of H. influenzae produce beta-lactamases, and are also able to modify its penicillin-binding proteins, so the bacteria have gained resistance to the penicillin family of antibiotics.

The bacterium's presence in these areas can lead to some conditions such as otitis media, chronic obstructive pulmonary disorder (COPD), epiglottitis, and asthma which can become severe.

[27] Effective vaccines for Haemophilus influenzae serotype b have been available since the early 1990s, and are recommended for children under age 5 and asplenic patients.

[58] The Hib vaccines do not provide cross-protection to any other H. influenzae serotypes like Hia, Hic, Hid, Hie or Hif.

[59] An oral vaccination has been developed for non-typeable H. influenzae (NTHi) for patients with chronic bronchitis, but it has not shown to be effective in reducing the number and severity of COPD exacerbations.