Table 1 The major pathogenesis factors of P. aeruginosa and therapeutics

Proteases

P. aeruginosa secreted proteases include elastase A, elastase B, large protease, protease IV, alkaline protease, Pseudomonas small protease, MucD, and P. aeruginosa aminopeptidase. They exhibit high proteolytic enzyme activity that damages host tissues by degrading proteins.

Protease inhibitors

Preclinical^369,392,408

Toxins

P. aeruginosa produces a variety of extracellular toxins, including pigments, phytotoxic factors, hydrocyanic acid, phospholipase, protein convertase, enterotoxin, exotoxin, and mucus. These exotoxins can cause leukopenia, acidosis, liver necrosis, pulmonary edema, circulatory failure, renal tubular necrosis and bleeding, and many other serious damages.

Bacteriophages

Preclinical^410,415,436

LPS

LPS is an integral component of cell envelope. It is the major virulence factor of P. aeruginosa and can be recognized by host pattern-recognition receptors to initiate inflammation and immunity response.

Antibody

Phase III^380,389,425

Pili and fimbriae

Pili and fimbriae are the major adherence factors. They contribute to the adherence and motility of P. aeruginosa in host.

Phages^380,422,424

None

Flagella

The main protein component of flagella is flagellin. Flagella provide motility and chemotaxis toward specific substrates and provide the ligand for clearance by phagocytic cells.

Bacteriophages

Phase III^366,393,410

Leukocidin (cytotoxin)

They are secreted by the typical secretion system (e.g., ExoU secreted by Type III secretion system) and are the main cytotoxin targeting lymphocytes and neutrophils.

Natriuretic peptides^376,380

None

Siderophores

There are two siderophores produced by P. aeruginosa: pyoverdine (formerly called fluorescein) and pyochelin. In addition to the iron needs, siderophores can support other virulence factors production by transferring iron, such as biofilms and toxic themselves.

Antibiotic-siderophore³⁸⁷

None

Urease

Urease enzyme is a virulence factor (limited extent) of P. aeruginosa. It can hydrolyze urea to produce ammonia and carbon dioxide (CO₂). It is associated with urinary tract infection.^378,427

None

None

Outer membrane proteins

The outer membrane contains a large number of outer membrane proteins. These protein members are involved in the transportation of amino acids and peptides, the absorption of antibiotics, and the transportation of carbon sources. They are essential for bacterial adherence, virulence secretion, and host recognition.

Potential receptor for the internalization of host

Phase I^372,456,457