User:Reaelise13/Haemophilus influenzae

Lead
Haemophilus influenzae (formerly called Pfeiffer's bacillus or Bacillus influenzae) is a Gram-negative, coccobacillary, facultatively anaerobic capnophilic pathogenic bacterium of the family Pasteurellaceae.The bacteria is mesophilic and grows best at temperatures between 35-37℃.

H. influenzae was first described in 1892 by Richard Pfeiffer during an influenza pandemic when he incorrectly described Haemophilus influenzae as the causative microbe, of the influenza pandemic, which is why the bacteria retains the name "influenza". H. influenzae is responsible for a wide range of localized and invasive infections, typically in infants and children, including pneumonia, meningitis, or bloodstream infections. Treatment consists of antibiotics, however H. influenzae has become resistant to the penicillin family, so ampicillin can be used in mild cases. The recommended form of prevention is a series of the Hib vaccine and boosters, which are most often given under the age of 5, and sometimes in conjunction with other vaccines in the form of the DTaP-IPV/Hib vaccine.

This species was the first free-living organism to have its entire genome sequenced.

Article body
Cases tend to present most often in children under the age of 5 more so than adults and older children. Many of the cases that are present in younger children begin to occur at around 2 years of age, with the mass majority of cases being seen in those around 4 years of age.

When children are admitted to the hospital for this sickness, there appears to be a correlation between the number of siblings the child has to the relative rate of catching this sickness. The correlation appears to be: the more siblings a child has, the more likely they are to contract this sickness.

Colonization of this bacterium is (change to still being studied?) an interesting point of study for this bacteria as well, with different age groups having different levels of colonization for this bacteria within them (needs to be reworded). Younger children (under the age of 6) can carry multiple strains of this same bacteria, while adults will typically carry just one.

Colonization nearly 100% of the time begins during the infant years of a child's life

We can also mention how healthy adults experience some level of colonization but it is less likely to be triggered as it is in children

This bacterium is opportunistic, meaning it enters the child, then is typically activated by a stressful event that triggers the bacterium to begin making the individual symptomatic. Some of those ways were briefly listed within the article:


 * Child injuring their head
 * kid choking on something and the bacteria was colonized in his upper airway
 * a child hurting her finger

Treatment options: we can talk more in depth about the breakdown of the vaccine for prevention and we can talk about the use of antibiotics and how that impacts this bacteria, as well as what that does to the colonization rates, and the strains that are colonized (all of that can be found in this article).

I found something in this article that briefly mentions the bacteria being present in the upper respiratory tract of healthy people and then the bacteria migrating downward to the lower respiratory tract where it then causes sickness. We could probably go into depth about how that works with the migration because this ties in with the colonization factor that i mentioned in one of the paragraphs above.

This could potentially have something to do with adhesion via autotransporters.

In adults, H. influenzae can cause bacterial bronchitis.

Environment
H. influenzae grows best in 5% CO₂ concentration. It is generally found within and upon the human body, but can also live on various dry, hard surfaces for up to 12 days.

Conjugation
Conjugative plasmids can frequently be found in H. influenzae. It is common that the F+ plasmid of an Escherichia coli bacterium conjugates into the H. influenzae bacterium, which then allows the plasmid to transfer among H. influenzae strands via conjugation.

Molecular methods
Polymerase chain reaction (PCR) assays have been proven to be more sensitive than either LAT or culture tests, and are highly specific. PCR testing can be used for capsular typing of encapsulated H. influenzae strains.

Other common tests used to culture this bacterial strain include simple blood tests, and spinal fluid tests, done by collecting cerebral spinal fluid from the lumbar region in the patients back.

Add section on structure of bacterium wall.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663868/

Other complications
otitis media, asthma, chronic obstructive pulmonary disorder - HI can infect many different areas in the body because it lives in different niches within the human body in healthy adults.

There are a few other possible diseases and conditions that can arise from the Haemophilus influenzae depending on the areas that they exist in within the human body. This bacterium can exist in the nasal passages (especially the nasopharynx), the ear canal, and the lungs. The bacterium's presence in these areas can lead to some conditions such as otitis media (which is the inflammation of the middle ear), chronic obstructive pulmonary disorder, which causes decreased air flow to the lungs, and asthma which can become severe .https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941224/#:~:text=influenzae%20uses%20a%20specialized%20type,of%20compounds%20including%20nitrite%20and Microbe page

https://microbewiki.kenyon.edu/index.php/Haemophilus_influenzae

Haemophilus influenzae colonization
Many microbes colonize within a host organism. Colonization occurs when a microorganism continues to multiply within the host, without interaction, causing no visible signs of illness or infection. Haemophilus influenzae colonizes differently in adults than it does young children. Because this bacterium colonizes more rapidly in young children, they are capable of carrying more than one strain of the same bacterium. Once in the adult stage of life, a human is likely to only be carrying one strain as this bacterium does not colonize as aggressively in adults. Nearly all infants will undergo colonization of this bacteria within their first year of life.

Physiology
some sources to look at for metabolism and cell wall:

https://www.sciencedirect.com/science/article/pii/S0960982202004785

https://onlinelibrary.wiley.com/doi/full/10.1002/prot.10057

https://journals.asm.org/doi/10.1128/JB.184.17.4868-4874.2002 (we can mention pili to adhere to host)

https://pubmed.ncbi.nlm.nih.gov/22919571/ (autotransporters)

Need to add motility(pili?), environment, cell wall, metabolism. Put name on which one you want to add.

Structure
H. Influenzae is a small gram negative bacteria, approximately .3 micrometer to 1 micrometer. Like other gram negative bacteria, H. influenzae have a thin peptidoglycan layer surrounded my an outer membrane containing lipopolysaccharide. Some types of H. influenzae contain a polysaccharide capsule around the outer membrane to aid in protection and colonization. The bacteria are pleomorphic, meaning the shape of the bacteria is variable, however it is typically coccobacillus or rod-shaped. It has also been found that Hib contains pili, which are specialized to adhere to the human nasopharynx. The Hib pili, unlike those of E. coli, resist unwinding, allowing for stronger adhesion to resist expulsion when coughing or sneezing. A minority of non-typeable, or unencapsulated, H. influenzae employ a variety of attachment techniques, such as pili, adhesins, or Hia and Hap proteins. Though the bacteria possesses pili, they are not used for traditional movement or motility, and the bacterium is still considered to be non-motile.

The cell wall of H. influenzae bacterium contains various proteins, referred to as autotransporters, for adherence and colony formation. H. influenzae prefers to bind to mucus linings or non-ciliated epithelial cells, which is facilitated by Hap𝘴 autotransporters in the cell wall binding with unknown receptors within the epithelium. The Hap𝘴 autotransporters also facilitate the formation of microcolonies of the bacteria. These microcolonies are likely responsible for the formation of various biofilms within the body, such as those which are responsible for middle ear or lung infections.

Metabolic pathways - i will add more to this later following more research
Extensive studies on the specific metabolic pathways of H. influenzae show that this bacteria has a blend of multiple pathways. It utilizes the Embden-meyerhof-parnass (EMP) specifically for glycolysis (glucose is broken down to create energy), and the Pentose Phosphate Pathway (PPP) specifically for dehydrating glucose (this allows for the utilization of glucose different from glycolysis for compounds such as carbohydrates). Many bacteria as we know, rely on the TCA cycle (tricarboxylic acid cycle) as it is one of the most important metabolic pathways for many different organisms as it provides energy to the organism, as well as aiding in aerobic respiration. Because the H. Influenzae bacteria has a number of diverse pathways to synthesize energy from, while it does contain and use the TCA cycle, it is incomplete and missing several enzymes that would be found in a fully functioning TCA cycle in another organism.

Reproduction: During reproduction, bacteria undergo a type of asexual reproduction called binary fission where the cell duplicates it genetic material and creates a new body of itself, by itself.

When Haemophilus influenzae exists within the body, it has been found in both aerobic, and anaerobic environments, as well as environments with different pH's. Knowing that this bacterium can survive in different environments, we know it needs to have the metabolic cabpabilites to do so. As we can see from the previous paragraph, we know that that is the case as this bacteria hosts a mixture of two pathways to function.

Penicillin Binding Proteins
Penicillin binding proteins (PBPs) contain penicillin binding domains are involved in peptidoglycan metabolism, which makes up the cell wall, to give bacterial cells rigidity. Beta-lactams are used in antibiotics that bind to PBPs, in order to target peptidoglycan synthesis. Some isolates of H. Influenzae have contained modified PBPs that resist beta-lactam action by producing beta-lactamases. This resistance is likely due to a N526K mutation, or R517H substitution in conjunction with another unknown mutation. The R517H substitution alone did not have a lower affinity for penicillin, and therefore cannot cause resistance alone. Beta-lactamase emergence in the 1970s caused the therapy for severe cases of H. influenzae to be changed from ampicillin to cephalosporins, however further resistance to cephalosporins has occurred due to changes in the transpeptidase domain of penicillin binding protein 3 (PBP3).

Serotypes
https://www.ncbi.nlm.nih.gov/books/NBK562176/ (good serotype explanation)

In 1930, two major categories of H. influenzae were defined: the unencapsulated strains and the encapsulated strains. Encapsulated strains were classified on the basis of their distinct capsular antigens. The six generally recognized types of encapsulated H. influenzae are: a, b, c, d, e, and f. H. Influenzae type b, also known as Hib, is the most common form, recognizable by it's polyribosyl ribitol phosphate (PRP) capsule, and found mostly in children. Types a, e, and f have been isolated infrequently, while types d and c are rarely isolated. Unencapsulated strains have a greater number of isolates and genetic diversity than the encapsulated group. Unencapsulated strains are termed nontypable (NTHi) because they lack capsular serotypes; however, they can be classified by multilocus sequence typing. 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).