Adhesin genes and serum resistance in Haemophilus influenzae type f isolates

Abstract

The incidence of invasive infections due to Haemophilus influenzae has decreased significantly in developed countries with high rates of vaccination against H. influenzae serotype b (Hib). This vaccine provides no protection against H. influenzae serotype f (Hif), typically associated with invasive infections in adults with chronic disease and/or immunodeficiency, and rarely in otherwise healthy adults and children. The specific properties of Hif associated with virulence remain largely uncharacterized. A panel of 26 Hif strains consisting of both invasive disease-associated and mucosal surface non-invasive disease-associated isolates was surveyed by DNA fingerprinting, biotyping and PCR detection of hmw1, hmw2, hsf, the hif fimbrial locus and the lipooligosaccharide (LOS) biosynthetic island, and assessment of b-lactamase expression and determination of resistance to the bactericidal activity of normal adult human serum. Repetitive sequence-based PCR fingerprinting differentiated the 26 strains into three clusters, with the majority of isolates (22/26, 84.6 %) clustered into a single indistinguishable group. Most isolates (24/26, 92.3 %) were of biotype I and two isolates produced b-lactamase with detection of a conjugative plasmid, and the isolates displayed a range of resistances to the bactericidal activity of human serum. All 26 isolates carried the adhesin hsf, 21 carried a partial hif fimbrial operon and 4 had the adhesin genes hmw1/2. A LOS biosynthetic island was detected in 20 isolates consisting of the genes lic2BC. It was concluded that Hif has many recognized virulence properties and comprises a relatively homogeneous group independent of the anatomical source from which it was isolated. INTRODUCTIONHaemophilus influenzae, a human-restricted Gram-negative coccobacillus, is a commensal of the upper respiratory mucosa and a pathogen commonly causing airway mucosal disease and occasional invasive disease. Since Margaret Pittman's original description of capsular serotypes among H. influenzae isolates in 1931 (Pittman, 1931), H. influenzae serotype b (Hib) had been the most clinically significant strain causing invasive disease (e.g. meningitis, epiglottitis, septicaemia and osteomyelitis) in previously well infants and children (Aubrey & Tang, 2003). Since the early 1990s, routine administration of the Hib conjugate vaccines (which induce protective levels of anti-capsular antibody) has virtually eliminated Hib disease among infants and young children in developed countries (Agrawal & Murphy, 2011;Ladhani, 2012). However, the vaccine provides no protection from infection due to nonb serotypes, including H. influenzae serotype f (Hif), which remains a rare but significant cause of invasive infection. Given the reduction in Hib carriage among Hib conjugate vaccine recipients, concern exists as to whether invasive disease due to Hif or other non-b encapsulated strains will become more prevalent due to serotype replacement Abbreviations: BLNAR, b-lactamase-negative ampicillin-resistant; CSF, cerebrospinal ...

Identification of a Haemophilus influenzae Factor H–Binding Lipoprotein Involved in Serum Resistance

“…The remaining challenges are to determine the relative part of each mechanism involved in bacterial serum resistance and their possible regulation, in particular at each step of the infection process. H. influenzae isolates collected from different anatomical localizations exhibit a comparable resistance against serum-mediated killing, suggesting that serum resistance is an important trait at every step, that is, bacterial adhesion followed by colonization, and finally invasion (67)(68)(69). Interestingly, we also showed that the H. influenzae-dependent affinity for complement regulators FH, C4BP and vitronectin was not higher in invasive strains as compared with isolates from the nasopharynx (67).…”

Adult-onset Invasive <i>Haemophilus influenzae</i> Type f Caused by Acute Lower Leg Cellulitis

“…H. influenzae can cause systemic infections in immunodeficient individuals. Thus, invasive disease associated with Hif appears to disproportionately affect individuals with underlying comorbidities, including adults suffering from chronic obstructive pulmonary disease, ethanol abuse, chronic renal disease, and immunodeficiency (14). Another pathogenetic feature of H. influenzae is the prevalence of β-lactamase expression (reportedly between 7.7% and 24.5%) (14).…”

“…Thus, invasive disease associated with Hif appears to disproportionately affect individuals with underlying comorbidities, including adults suffering from chronic obstructive pulmonary disease, ethanol abuse, chronic renal disease, and immunodeficiency (14). Another pathogenetic feature of H. influenzae is the prevalence of β-lactamase expression (reportedly between 7.7% and 24.5%) (14). However, in keeping with the present case, the literature on β-lactamase non-producing ampicillin-resistant strains (BLNAR) and β-lactamaseproducing amoxicillin-clavulanate-resistant (BLPACR) isolates includes few reported cases of Hif.…”

A Fine-Tuned Interaction between Trimeric Autotransporter Haemophilus Surface Fibrils and Vitronectin Leads to Serum Resistance and Adherence to Respiratory Epithelial Cells

“…Hia is present only in approximately 25% of clinical NTHi isolates (10) and cannot be found in encapsulated H. influenzae. In contrast, the Hia homologue Hsf exists in all typeable strains (11)(12)(13). Although Hia has a smaller size of Ϸ114 kDa (Ϸ342 kDa as a trimer), these two proteins are highly homologous at their N and C termini, with an overall 81% similarity and 72% identity.…”