Haemophilus aegyptius

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1. Classification

a. Higher order taxa Bacteria, Proteobacteria, Gamma Proteobacteria, Pasteurellales, Pasteurellacease, Haemophilus (1)

b. Species Haemophilus Influenzae (1)

2. Description and significance

Haemophilus influenzae biogroup aegyptius is a Gram-negative bacterium with an elongated rod shape (2). H. aegyptius is normally found living in human epithelial cell linings (10), where it exhibits colonization and adherence to epithelial cells with large clusters of elongated chains of cells (2). As a biogroup, H. influenzae biogroup aegyptius has traits that differ from Haemophilus influenzae (H. influenzae), including the severity of virulence and lack of genes that encode for a polysaccharide capsule (3) in H. influenzae biogroup aegyptius. For over a century since its first discovery, H. influenzae biogroup aegyptius had only been known to cause conjunctivitis. However, in 1995, the HaeBPF strain of H. influenzae biogroup aegyptius (3) was identified in patients with Brazilian Purpuric Fever (BPF) (4). BPF has symptoms that are similar to that of meningococcal sepsis, which include an infection that results in high fever, vomiting, abdominal pain, and hemorrhagic skin lesions (5). Researchers have spent over two decades learning about the transformation of H. influenzae biogroup aegyptius from causing mild conjunctivitis to deadly BPF. However, much is still unknown about the organism’s virulence factors (6). Because of this, studies have been focused on understanding the mechanism of pathogenesis and developing preventative measures and treatments for BPF.

3. Genome structure

The Haemophilus influenzae biogroup aegyptius genome, or F3031 genome, contains 77% shared sequences with other H. influenzae genomes (4). The Hae accessory genome sequences were delineated and 163 protein-coding genes were characterized as adhesins and fimbrial operons (3). The Haemophilus influenzae biogroup aegyptius genome includes 3031 plasmids, and sequences coding for pilin proteins (6).

Unique genes sequences to the genome of H. influenzae biogroup aegyptius are: the bpf001 and bpf002 genes, which are associated with Brazilian Purpuric Fever (BPF) (4), and the Haemophilus adhesin A gene (HadA) (7). bpf001 and bpf002 code for proteins that enhance epithelial cell entry, correlating with cell invasion of human respiratory epithelial cells during the pathogenesis of BPF (4). The HadA gene codes for an adhesion protein that is associated with adherence to extracellular matrix proteins of human cells during the onset of BPF (7).

There has been evidence of exchange of the Las gene between H. influenzae biogroup aegyptius and Neisseria meningitidis, a bacterium that causes brain and spinal cord inflammation (5).

4. Cell structure

Unique to the H. influenzae biogroup aegyptius’s cell structure is an oliogomeric coiled-coil adhesion (Oca) adhesion called HadA (Haemophilus adhesion A), an adhesion protein. HadA allows bacterial aggregation when present in liquid culture, possibly through intrinsic hydrophilic properties and promotion of bacterial attachment to and invasion of host cells (7). These phenotypic properties of HadA are associated with cell invasion in the pathogenesis of Brazilian Purpuric Fever (BPF).

During interaction with epithelial cells, H. influenzae biogroup aegyptius exhibits colonization and adherence to epithelial cells with large clusters of elongated chains of bacterial cells. This clustering of H. influenzae biogroup aegyptius is unlike H. influenzae, which organizes by an even distribution as individual coccobacilli on epithelial cells (2).

5. Metabolic processes

Haemophilus influenzae biogroup aegyptius has metabolic characteristics similar to H. influenzae in metabolizing sugars. H. influenzae metabolizes fructose using phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) (8). When there is a scarcity in available fructose, H. influenzae transports and metabolizes fucose using fuculokinase, which is coded by an operon unique to H. influenzae (9).

A notable difference of H. influenzae biogroup aegyptius, compared to other H. influenzae strains, is its inability to ferment xylose and its inability to produce indole (9). Inability to produce indole is an implication that H. influenzae biogroup aegyptius lacks the enzyme tryptophanase (9), which is present in other H. influenza strains. H. influenzae biogroup aegyptius also exhibits urease activity, but lacks ornithine decarboxylase activity (2).

6. Ecology

H. influenzae biogroup aegyptius is normally found as an inhabitant of human epithelial cell linings (10) such as the oropharynx (1) and the epithelial layer of the eyes, where it presents as conjunctivitis (4). The manifestation of H. influenzae biogroup aegyptius has been identified as the disease-causing agent of BPF (11) in children and adults.

7. Pathology

Haemophilus influenzae biogroup aegyptius has been most commonly linked to cases of acute conjunctivitis and Brazilian Purpuric Fever (BPF) (6). A particular strain of H. influenzae biogroup aegyptius known as Hae causes conjunctivitis. Conjunctivitis is a disease more commonly known as “pink eye” that induces inflammation in the eye (3). The strain of Haemophilus influenzae biogroup aegyptius that is linked to BPF is known as HaeBPF.

The first outbreak of BPF occurred in Sao Paulo State, Brazil in 1984 (3) followed by several hundred cases that occurred sporadically. The outbreaks were occurring mainly in small towns (3) in Brazil including Presidente Prudente, Fartura, Sao Jose do Rio Preto, Serrana, Guatapara, and Promissao (1). Three other cases that were reported: two in Australia (4) and one in United States, specifically in Connecticut (11).

HaeBPF was first identified and characterized during the second outbreak of BPF that occurred in 1995 (3). The onset of BPF uniquely occurs in individuals that previously contracted pus-containing conjunctivitis that was eventually resolved (3). However, these individuals later develop bacteremia, the presence of bacteria in the blood, when H. influenzae biogroup aegyptius enters the bloodstream (12). This disease predominantly affects infants and young children under the age of 10, producing symptoms such as high fever, abdominal pain and vomiting, skin lesions, and vascular collapse, from which can lead to death (6). On the cellular level, BPF is characterized by cytotoxicity in endothelial cells caused by H. influenzae biogroup aegyptius (13).

The mechanism through which Haemophilus influenzae biogroup aegyptius infects and causes disease has not been well defined. Adhesins for binding and other BPF-specific outer membrane proteins have been identified, but their roles in virulence and pathogenicity are not clear (3).

Although the BPF strain of Haemophilus influenzae biogroup aegyptius is generally pathogenic and can lead to serious symptoms, studies have indicated that older children and adults who were exposed to the bacteria were able to develop serum bactericidal antibodies against BPF strains (14). As a result, they experienced no particular symptoms. Also, there was evidence of immunity from BPF through high levels of antibodies in children who had conjunctivitis caused by the BPF strain of Haemophilus influenzae biogroup aegyptius but did not develop BPF (14).

There is currently no established treatment for Brazilian Purpuric Fever; however, Haemophilus influenzae biogroup aegyptius is sensitive to antibiotics such as ampicillin and chloramphenicol (6), and research suggests that early antimicrobial treatment may improve chances of survival (15).

7. Epidemiology

In Brazil, around 90% of individuals who developed Brazilian Purpuric Fever did so after recovering from conjunctivitis (6). Case control studies have been performed in three towns in Brazil-- Promissao, Londrina, and Serrana-- to investigate the relatedness between the two diseases. These studies found an association between conjunctivitis and BPF (6). Other case control studies were carried out to determine risk factors for BPF. Day care attendance appeared to be a significant risk factor for BPF (6).

8. Current Research

Current research focuses on how H. influenzae biogroup aegyptius emerged as a virulent strain, causing Brazilian Purpuric Fever (BPF). Since horizontal transfer of virulence genes between Haemophilus influenzae and Neisseria meningitidis has been noted in the past, the genome sequences of H. influenzae biogroup aegyptius and N. meningitidis (5) were compared. A genetic sequence unique to N. meningitides, NMB0418, was identified in the genome of a H. influenzae biogroup aegyptius strain associated with BPF (5). When cells that contained an antibiotic interacted with a H. influenzae biogroup aegyptius strain that expressed the NMB0418 sequence, the antibiotic-containing cells had a higher inflammatory response than when they were exposed to the N. meningitidis strain (5). This indicated that there might be other genetic sequences that influence the expression of an inflammatory response during the onset of BPF.

9. References

It is required that you add at least five primary research articles (in same format as the sample reference below) that corresponds to the info that you added to this page. [Sample reference] Faller, A., and Schleifer, K. "Modified Oxidase and Benzidine Tests for Separation of Staphylococci from Micrococci". Journal of Clinical Microbiology. 1981. Volume 13. p. 1031-1035.