Haemophilus influenzae

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Classification

Bacteria; Proteobacteria; Gamma Proteobacteria; Pasteurellales; Pasteurellaceae; Haemophilus

Species: H. Influenzae. (Binomial name: Haemophilus Influenzae)

Other Species: H. aegyptius; H. aphrophilus; H. avium; H. ducregi; H. felis; H. heamolyticus; H. paracuniculus; H. parahaemoluticus; H. pittmaniae; etc…

Description and Significance

Haemophilus influenzae is a bacterial inflection in the blood stream. It was first isolated by Pfeiffer during the 1890’s around the influenza pandemic tie period. Haemophilus influenzae grows best around 35-37 degree with a pH level of 7.6 and a specific growth factor that can be found in the blood stream. In labs this bacteria can be grown under aerobic conditions with 5 % CO2 tension in the atmosphere. Since 1988 a more serious strain of bacteria H. influenzae type b had been abolish in the U.S. due to effective vaccine development. H. influenzae type b causes meningitis, which is an inflection in the membrane around the brain and epiglottitis which is infection around the throat and trachea. In general H. Influenzae bacteria lives in the upper respiratory tract which can be transmitted by close contact with patients. This bacterial infection can also be air born transmitted through sneezing.

Genome Structure

H. influenzae became the first free-living organism with its entire genome sequenced. Its genome consists of 1,830,140 base pairs of DNA and contains 1740 genes. The linear DNA sequence of bacterial chromosome gives information, identifying all potential open reading frames, intergenic sequences, and their orgainzation within the genome. (5) The genome of these bacteria contains information on the genetic basis for each influencing host. The H. influenzae genome sequence provides the starting opint for significant research on bacterial metabolism, host adaptation, and virulence. Analysis of the genetics of biosynthesis and biology of LPS (lipopolysaccharide) in H influenzae indicated shows that LPS has complex cell surface glycolipid. (5) The saccharide portion of H. influenzae LPS is involve in host cell interaction and the lipid A portion of the molecule, the endotoxin, iitiates the cytokina casade as part of the host response to infection.

Cell Structure and metabolism

Haemophilus influenzae is a small gram negative bacteria which is about 1x 0.3um in size and it also lack the presence of flagella and pili, which means it lack mobility. (6) Some of these bacteria contain polysaccharide capsule which function as protection and colonization. These bacteria resemble other gram negative bacteria in structure, composition and endotoxic activity. The cell wall has an ultra structure composed of multiple wavy outer membranes and a poorly defined plasma membrane with an intervening electron transparent space. The outer cell wall has vesicular structure which is morphologically identical to lipopolysaccharide vesicles and are excreted into the surroundings. “Encapsulated strains express one of six structurally and antigenically distinct polysaccharide capsules, designated serotypes a to f.” (5) This bacteria is generally aerobic, but can grow as a facultative anaerobe.

Pathology

Haemophilus influenzae requires two growth factor which are X (hemin) and V (nicotinamide-adenine-dinucleotide). These two factors are related to the red blood cell, therefore when infection occurs red blood cell the first infected area resulting in the idea that humans are the only natural hosts. Haemophilus influenzae, also know as H. influenzae, "is a common resident of the nasopharyngeal mucosa and, in some instances, of the conjunctivae and genital tract."(3). H. influenzae is commonly transmitted by direct contact also can be transmitted by inhalation of the respiratory tract droplets. It is known that having a large load of bacterial or the presence of a concomitant viral infection can potentate the infection. The colonizing bacteria invade the mucosa and then enter the bloodstream and spread to the rest of the body, creating a infection. The host defenses for h. influenzae include the pathways and antibodies to the PRP capsule. The primary role of the immunity defense is the antibody to the Hib capsule which plays a role in conferring immunity. Due to this new born babies have low risk for this inflection. However high risk for new born babies for h. influenzae disease occurs when "maternal antibodies transplacental antibodies to the PRP antigen wane"(3) and due to this their immune system response to infections lowers even after they had the disease which results in repeated infections to possible occur. This is due to the fact that the first time of contacting this infection h. influenzae do not confer immunity. "The Hib congugate vaccine induces protection by inducing antibodies against the POP capsule."(3) However this vaccine does not protect host from nontypeable strains. Nontypeable h. influenzae is transmitted by "direct extension of the Eustachian tubes which causes otitis media."(3) When this is inflected to the sinuses it will lead to sinusitis. When this inflected the respiratory tract, bronchitis and pneumonia occur in host. Other possible events that would cause an inflection are "Eustachian tube dysfunction, antecedent viral upper respiratory tract infection (URTI), foreign bodies, mucosal irritants, and smoking."(3) When this inflection inflects invade a host with "underlying chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF) this disease frequently colonizes the lower respiratory tract and can exacerbate the disease."(3) This specific type of disease, nontypeable h. influenzae, can form biofilm in vitro and ex vivo. By studying about the structure of the biofilm and its protein can help researchers find and develop new ways to fight this disease. When inflected with haemophilus influenzae different children will show different symptoms, the symptoms also depends which part of the human body has been infected. For infection of otitis media, the middle ear inflection, some of the symptoms are difficult sleeping or staying asleep , fever, fluid draining from either one or both ears, loss of balance, hearing difficulties, ear pain, nausea, vomiting, diarrhea, lost of appetite, and congestion. For infection in the eye, conjunctivitis which in the infection of conjunctiva, which is a membrane that lines the inside of the eye, some of the most common symptoms are redness, swelling, drainage from one eye or sometimes both, burning of eyes, and sensitive to brightness or light. For infection in the sinuses, sinusitis, symptoms for younger children are runny nose lasting more then 10 days, night time cough, sometimes day time cough, swelling around the eyes, and headaches. For older children the symptoms may include runny nose, cold symptoms lasting more then 10 days, drips in throat from nose, headaches, facial discomfort, bad breath, cough, fever, sore throat, and swelling around the eyes. For inflection in the throat, epiglottises, starting symptoms are sore throat, fever, muffled voice, and cough. As the infection worsens, drooling starts, unable to talk, leaning forward while sitting, and keeps mouth open without knowing. For infection in the membrane that surround the brain and spinal cord, meningitis, the symptoms for children older then 1 year, nect pain, back pain, headache, nausea, vomiting, and stiffness in the neck. In infants usually the symptoms are irritability, sleeping all the time, refusing a bottle, cries when picked up or being held, inconsolable crying, soft spot, and its behavior changes. These are some of the general symptoms but these symptoms may not also pinpoint the presence of this infection because these symptoms may also represent other infection so for a more accurate diagnose consults a physician for positive infection. When being diagnose a basic chest or neck x-ray along with a blood tests may be required by most physician. Treatment for this infection depends on where the infection is located at, the age of the patient, and the patient's medical history. One way to treat this is by taking antibiotics however the length of this type of treatment depends on severity of the infection. To prevent this infection is to obtain "immunization against type b, which is the most invasive strain of H. influenzae, is routinely administered in a 3 to 4 part series shots."(8) These shots are given to new born starting at 2 month old, then the 2nd shots is given at 4 month, then 3rd shots at 6month. Then a booster is usually given when the infant is around 12 to 15 month old. This is the basic prevent that all infant should receive prior to age of 5.

Application to Biotechnology

This organism does not produce any useful compounds or enzymes that can help or benefit any other organisms.

Current Research

One of the current research that is going on today is done by the CCRI research team, which is led by Robert Munson, Jr., Ph.D. from center for microbial pathogenesis. This research team is current conducting an experiment which can complete the genome sequence for a strain of nontypeable Haemophilus influenzae. By farther understanding of the genome sequence for nontypeable Haemophilus influezae can allow the people today to understand the basic genetic makeup of this organisms. By understanding this it allows us to know more about this disease and how to prevent it. It can also allow current researcher to farther perform experiment that could lead vaccine or novel interventions. (9) Another research is from the Brazilian Journal of Medical and Biological Research. In this research cerebrospinal fluid (CSF) was isolated from hospitalized patients whom were infants and young children. From the fluids that were collected it was suggested that “ceftriazone could be an option for the treatment of bacterial meningitis in pediatric patients who have not been screened for drug sensitivity.” (10) This was concluded after some experiment done on the CSF collected, these experiments were bacterial strains, strain identification, susceptibility testing, and beta-lactamase assay. Another research is done by Arnold Smith, M.D. from Seattle Biomedical Research institute. In this research, Dr. Smith’s purpose is to understand how this bacterium causes diease, which can help improved current treatments and preventions. In the lab molecular mechanisms of h. influenzae was understood. It was also noted that specific strains of this bacteria have ability to cross the respiratory tract of young children. It was also found that once this infection enter the blood stream it may cause sepsis and meningitis. This research is currently in progress at the Seattle Biomedical Research Institute. (11)

References

1. Hans Gmuender, Karin Kuratli, Karin Di Padova, Christopher P. Gray, Wolfgang Keck, Stefan Evers. “Fene Expression Changes Triggered by Exposure of Haemophilus influenzae to Novobiocin or Ciprofloxacin: Combined Transcription and Translation Analysis” Genome Research. 2001. Vol. 11, Issue 1, 28-42. http://www.genome.org/cgi/content/full/11/1/28

2. http:/lib.bioinfo.pl/avid:1681

3. Vidya R Devarajan, MD, Wesley W Emmons, Francisco Talavera, PharmD, PhD, Charles V Sanders, MD, Eleftherios Mylonakis, MD, PhD, Burke A Cunha, MD, MACP. “Haemophilus Influenzae Infections” eMedicine from WebMD. January 16,2007. http://www.emedicine.com/med/topic 936.html

4. “ Haemophilus influenzae Serotype B (Hib) Disease” Centers for Disease Control and Prevention. October 11, 2005. http://www.cdc.gov/Nip/publications/surr-manual/chpto2_hib.pdf.

5. Mark A. Herbert, Derek W. Hood, E. Richard Moxon “Haemophilus influenzae Protocols” Humana Press, Totowa, New Jersey. 2003.

6. Gabriel Waksman, Michael Caparon, and Scott Hultgren “Stuctureal Biology of Bacterial Pathogenesis” ASM Press, Washington, D.C. 2005.

7. J E Foweraker, N J Cooke, and P M Hawkey “Ecology of Haemophilus influenzae and Haemophilus parainfluenzae in sputum and saliva and effects of antibiotics on their distribution in patients with lower respiratory tract infections.” PubMed Central Journal List v. 37(4); April 1993. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=187767

8. http://www.healthsystem.virginia.edu/uvahealth/peds_infectious/hii.cfm

9. “Medical News Today: Genome Sequence for Haemophilus Influenzae Completed” 8/22/2005 http://www.medicalnewstoday.com/medicalnews.php?newsid=29468

10. “Sciflo Brazil: Brazilian Journal of Medical and Biological Research: Antimicrobial resistance patterns of Haemophilus influenzae isolated from patients with meningitis in Sao Paulo, Brazil” 12/19/1999. http://www.scielo.br/scielo.php?pid=S0100-879X2000000300006&script=sci_arttext

11. Arnold Smith, M.D. “Seattle Biomedical Research Institute” 2007. http://www.sbri.org/research/a_smith.asp