Contribution of an arsenal of virulence factors to pathogenesis of Pseudomonas aeruginosa infections

Abstract

Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of nosocomial infections, life-threatening diseases in immunocompromised persons and chronic pulmonary infections in cystic fibrosis patients. The organism's virulence depends on an arsenal of cell-associated and extracellular factors determining the pathogenesis of infections as multifactorial. Most P. aeruginosa infections are both invasive and toxinogenic. Many of the extracellular virulence factors (proteases, exotoxin A, pyocyanin, siderophores, hemolysins) required for tissue invasion and dissemination of P. aeruginosa are controlled by quorum sensing (QS) that enable the bacteria to produce these factors in a coordinated, cell-density-dependent manner and overwhelm the host defense mechanisms during acute infection. Sometimes, QS also contributes to biofilm formation and thus participates in pathogenesis of chronic infection. This system is recognized to be a global regulatory network controlling the expression of a large number of virulence genes either directly or indirectly. Two-component sensor kinases such as RetS, LadS and GacS are also controlling the production of virulence factors as well as the switch from acute to chronic infection. The present review describes the known virulence determinants of P. aeruginosa, the stages of infection as well as the importance of QS in the pathogenesis of P. aeruginosa infection.

Staphylococcus aureus Alters Growth Activity, Autolysis, and Antibiotic Tolerance in a Human Host-Adapted Pseudomonas aeruginosa Lineage

“…A total of 100 l of P. aeruginosa overnight culture (diluted to OD 600 ϳ 0.2) was spread on top of LB agar plates, containing different concentrations of tobramycin (i.e., 0, 5, 10, 12.5, 14, 15, 16, 17.5, and 20 g/ml), gentamicin (i.e., 10,15,20,25,30,35,36,37,38,39, and 40 g/ml), and ciprofloxacin (i.e., 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, and 10 g/ml) and left to dry under a lid for 30 min. Wells were prepared in the P. aeruginosa-covered agar plates by removing 6-mm agar plugs.…”

“…In addition, P. aeruginosa exoproducts were found to inhibit S. aureus respiration, induce resistance toward antibiotic killing (9), and stimulate pigment (e.g., staphyloxanthin) production, virulence, and biofilm formation by S. aureus (10)(11)(12). The virulence mechanisms of P. aeruginosa and S. aureus and their regulation have been widely studied (13)(14)(15). In P. aeruginosa, the majority of the extracellular virulence factors are controlled by the Pseudomonas quorum sensing (QS) system, which consists of two hierarchical systems, las and rhl, induced by cell density-dependent acyl-homoserine lactone (AHL) signaling molecules.…”

“…In P. aeruginosa, the majority of the extracellular virulence factors are controlled by the Pseudomonas quorum sensing (QS) system, which consists of two hierarchical systems, las and rhl, induced by cell density-dependent acyl-homoserine lactone (AHL) signaling molecules. In addition, the 4-hydroxy-2-alkylquinoline (HAQ) molecule 3,4-dihydroxy-2-heptylquinoline (PQS) and its biosynthetic precursor 4-hydroxy-2-heptylquinoline (HHQ) act as signaling molecules regulating the Pseudomonas QS system (15)(16)(17). The transcriptional regulator LasR controls the conversion of HHQ to PQS, thereby providing a link between the AHL and HAQ regulatory systems (17).…”

Phage Therapy: a Step Forward in the Treatment of Pseudomonas aeruginosa Infections

“…aeruginosa possesses an arsenal of virulence factors enabling it to invade host cells and circumvent host defenses (35,42). These mechanisms of virulence include secreted factors such as proteases, elastase, pyocyanin, exotoxin A, phospholipase C, and exoenzyme S and also cell-associated factors such as lipopolysaccharide (LPS), flagella, and pili (35,43). Many of these virulence factors are controlled by a cell-cell communication mechanism known as quorum sensing (QS), which allows bacteria to produce these factors in a cell density-dependent manner (35,43,44).…”

Bactericidal Efficiency and Modes of Action of the Novel Antimicrobial Peptide T9W against Pseudomonas aeruginosa

“…Among the resistant bacteria, the Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that infects a wide range of animal, plant, and human hosts (4). Compared with other pathogens, P. aeruginosa is very difficult to eradicate because it displays high resistance to a wide variety of antibiotics, including aminoglycosides, fluoroquinolones, and ␤-lactams, largely because of the low permeability of its outer membrane, which limits the rate of penetration of antibiotic molecules into the cells (5).…”