Pseudomonas aeruginosa
John Rule
My microbe is Pseudomonas aeruginosa, the most common gram-negative bacterium found in nosocomial infections.  Some basic information is that it comes from the Pseudomonadaceae family, and is a motile, gram-negative, aerobe rod.  It lives primarily in water, soil and vegetation.  This pathogen is viewed as opportunistic since it has the ability to spread abundantly but doesnít except in immunocompromised patients.

A group of these people are patients with neutropenic cancer or bone marrow transplant patients.  P. aeruginosa is responsible for 30% of the deaths in these people, usually from the development of either pneumonia or septicemia.  Burn patients are another common group to encounter this problem, with P. aeruginosa accounting for 60% of the death rate.  It is also associated with 50% of the deaths in the AIDS population.  Chronic infection in cystic fibrosis is responsible for the deadly illness that occurs.

One reason that P. aeruginosa is an opportunist pathogen is that it is deficient in the ability to carry out the initial steps of infections.  To initiate the infection there must be a break in the first-line defenses (due to trauma, surgery, serious burns, defects from cystic fibrosis and AIDS sysdrome).  An important thing for colonization by P.aeruginosa is the ability to adhere to epithelial cells, by using things like flagella, which are usually responsible for motility.  There are other processes responsible for adheson but most are still unclear.

The ability of these bacteria to produce overwhelming infections is due to its arsenal of virulence factors and excreted enzymes.  These extracellular products cause extensive tissue damage, bloodstream invasion, and dissemination, as shown in Figure 1 (2).  I will discuss some of the more prevalent extracellular virulence factors.  Exotoxin A is responsible for local tissue damage, bacterial invasion and immunosuppression.  Exotoxin A catalyzes ADP-ribosylation and inactivation of elongation factor 2 which leads to inhibition of protein biosynthesis and cell death.  Exoenzyme S is responsible for tissue destruction in lung infection.  Exoenzyme S is produced by the bacteria growing in the burned area and is detectable in blood before the bacteria is.  This enzyme may also be important in bacterial dissemination.  A hemolysin, Rhamnolipid, a rhamnose-containing glycolipid biosurfactant, has a detergentlike structure that is able to dissolve phospholipids of the lungs making them able to be cleaved by phospholipase C.  P.aeruginosa also produces some proteases (LasB elastase,LasA elastase and alkaline protease) which are able to destroy the protein elastin (which is a big part of human lung tissue which is responsible for lung expansion and contraction).

An extremely interesting aspect of P. aeruginosa is itís ablility to do Cell-to-Cell signaling.  Through this cell-to-cell signaling the bacteria is able to control the production of its extracellular virulence factors and control cell density.  One of the best known cell-to-cell signaling systems is the lux system in Vibrio fischeri, which responds to the cell-density.  In P. aeruginosa the cell-to-cell system is called the las system, because it regulated the expression of LasB elastase.  This system is composed of lasI and lasR.  The las system also helps in the optimal production of other extracellular virulence factors like LasA protease and exotoxin A.  The las system also activates the xcpP and xcpR genes that encode for the secretory pathway for P. aeruginosa.  The las system is positively controlled by GacA and Vfr, and inhibited by RsaL.  A second cell-to-cell signaling system is the rhl system.  Thus named for its ability to control the production of rhamnolipid.  This system is composed of rhl1 and rhlR genes.  The rhl system regulates the expression of rhlAB operon that is required for rhamnolipid production.  For the optimal production of LasB elastase, LasA protease, pyocyanin, cyanide and alkaline protease the rhl system is required.  For the optimization characteristics of the las and rhs cell-to-cell signaling systems they are called virulence secondary metabolites.  These two systems regulate the expression of various extracellular virulence factors.  Another interesting fact is that the las and rhl signaling systems interact.  The importance of cell-to-cell signaling is that through the coordinated expression of virulence genes by the entire bacterial population they secrete extracellular factors only when they could be useful, thus allowing it to overcome host defense mechanisms and save its strength for when it could efficiently fight.

One aspect of the P. aeruginosa pathogen that I found extremely interesting is that mucoid mutants produce a exopolysaccharide called alginate.  They produce a slime matrix, a biofilm (which are microcolonies surrounded by an exopolysaccharide) in which the mutant bacteria grows.  This biofilm is resistant to antibiotics and disinfectants, which allows the bacteria to survive in harsh conditions.

The last topic Iíll discuss is this bacteria high resistance to antibacterial drugs.  P. aeruginosa is a particularly dangerous pathogen due to the fact that few antibiotics are effective (a few effective ones are fluoroquinolones, amikacin and gentamicin, and certain broad-spectrum Beta-lactam antibiotics like imipenim).  Resistance is due to outer membrane permeablility or mulitdrug efflux pumps, and the ability of it to create new resistant strains on exposure to antibiotics.  This is especially a problem in cystic fibrosis patients.  Since itís difficult to deal with P. aeruginosa directly, a tempting approach is to reduce the production of extracellular virulence factors.  Also, as elements that are essential for the synthesis of autoinducers become known, drugs inhibiting the biosynthesis process could be designed.  Also, drugs that interfere with biofilm differentiation could make these colonies more susceptible to antibiotics and biocides.

Works Cited

(1) Abigail A Salyers and Dixie D. Whitt, Bacterial Pathogenesis: A molecular approach, ASM press 1994, chapter 21: pages 260-268.
(2) Christian Van Delden and Barbara H. Iglewski, Cell-to-Cell Signaling and Pseudomonas aeruginosa Infections, found on the web at the CDC website.


 

*Disclaimer - This report was written by a student participaring in a microbiology course at the Missouri University of Science and Technology. The accuracy of the contents of this report is not guaranteed and it is recommended that you seek additional sources of information to verify the contents.

 

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