Pseudomonas aeruginosa

The group of pathogens that hold the leadership positions as causative agents of human hospital-acquired (or nosocomial) infections comprises aerobic nonfermenting gram-negative bacteria. The related microbial families of Pseudomonadacea, Xanthomonadaceae, Moraxellaceae, and Burkholderiaceae belong to these bacteria.
The highest clinical relevance is demonstrated within this group by a limited number of microbial species, namely Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. In patients of intensive care units, burn centres and surgery departments, they provoke serious complications, suppurative and wound infections. In addition, all of them show extreme levels of antimicrobial agent resistance.
The most common life-threatening pathogen is Pseudomonas aeruginosa. It is usually a saprophytic microbe that can foam on human skin and mucosal tissues, but causes severe outbreaks of nosocomial infections, particularly in patients with immunity suppression.

Discovery Pseudomonas aeruginosa

Initial description of Pseudomonas aeruginosa was presented by French pharmacist Carle Gessard as far back as in 1882. Similarly, the first representatives of Acinetobacter genus were discovered by M.W. Beijerinck in 1911. Nevertheless, active study of multidrug-resistant acinetobacters, e.g., Acinetobacter baumannii, commenced only from the early 1990s. The first type strain of Stenotrophomonas maltophilia was isolated in 1958 by R. Hugh.

Classification of Nonfermenting Gram-negative Bacteria

  • Pseudomonas aeruginosa is in the Pseudomonadacea family of the Pseudomonas genus.
  • A member of the family Xanthomonadaceae is Stenotrophomonas maltophilia.
  • The pathogens of the genus Acinetobacter A. baumannii and A. baylyi belong to the Moraxellaceae family.
  • Finally, hospital-acquired infections are caused by pathogenic representatives of the Burkholderiaceae family Burkholderia cepacia; zoonotic agents B. mallei cause glanders and B. pseudomallei-melioidosis.

Structure and Properties of Pseudomonas aeruginosa


The major pathogen from the group of non-fermenting gram-negative bacteria is Pseudomonas aeruginosa. Small gram negative rods measuring around 2 μm are pseudomonads. They are single motile bacteria with one polar flagellum, non-spore forming. Multiple fimbriae and pili promote epithelial cell microbial attachment. Typically isolated from cystic fibrosis patients, multiple mucoid strains produce large amounts of alginate exopolysaccharide that envelops bacterial cells.


On basic nutrient media, Pseudomonads grow well. At 42°C, P. aeruginosa can propagate.
Smooth or mucoid circular greenish colonies are displayed during cultivation of P. aeruginosa. The colour of colonies results from the overproduction of pyocyanin with non-fluorescent bluish pigment; to a lesser extent, the bacteria produce pyoverdin with fluorescent green pigment, pyorubin with ruby colour or pyomelanin with black pigment.

Due to the extensive production of adhesive exopolysaccharides, all pseudomonads actively form biofilms on adjacent surfaces. Hemolysis can be caused by certain P. aeruginosa isolates. Selective P. aeruginosa culture media contain a variety of substances (e.g., cetrimide or acetamide) that promote selective pseudomonad growth.

Biochemical properties

Mandatory aerobes are pseudomonads. They don’t ferment, but glucose oxidizes. Oxidase and catalase are produced by these bacteria. S. aeruginosa, without the formation of H2S or indole, liquefies gelatin and hydrolyzes casein and reduces nitrates to nitrites.

Antigenic structure

Antigenic epitopes of pseudomonads are localized predominantly within lipopolysaccharides of the cell wall (group-specific somatic O-Ag) and microbial flagellar proteins (type-specific H-Ag).

Virulence factors

The broad scope of virulence factors is expressed by S. aeruginosa. The bacteria have the structures of secretion systems of type II, III and VI that deliver virulence proteins into affected cells. Several adhesins promote tight microbial attachment to the tissues and cells. Bacterial exopolysaccharides protect bacteria against phagocytosis and create the basis for the formation of biofilms.

Cell wall lipopolysaccharides have an endotoxin activity. S.aeruginosa synthesises exotoxin A which blocks protein synthesis by ribosylation of cell elongation factor 2 (EF-2). Exotoxins ExoU (phospholipase), ExoY (adenylate cyclase), ExoS and ExoT (ribosyltransferases) inhibit cell separation after division (cytokinesis) and therefore significantly impede wound healing. Hemolysins (phospholipase C and lipase) directly damage the cell membrane. The variety of aggressive exo-enzymes (collagenase, elastase, proteases) destroys the connective tissue components and intercellular tight junctions. Neuraminidase hydrolyzes the host of sialic acids.

Microbial siderophores supply the bacterial cells with iron. Most pseudomonads produce bacteriocins (pyocins). Finally, P. aeruginosa has remarkable and highly versatile mechanisms for natural multidrug resistance to antibiotics, antiseptics and disinfectants. For example, the primary mechanism of resistance is based on the extremely poor permeability of bacterial LPS to β-lactam antibiotics. They can only be transported across the cell wall through the pore channels within the bacterial envelope. Frequent mutations of porin proteins lead to a blockage of the entry of β-lactam into microbial cells.

In addition, P. aeruginosa maintains extensive reverse transport (or efflux) of antimicrobial agents outside the microbial cell. At least 4 separate efflux systems provide active backward transport of multiple antibiotic classes – β-lactams, fluoroquinolones, aminoglycosides, and tetracyclines. In addition, P. aeruginosa express β-lactamase enzymes encoded with chromosomal and plasmid genes. Among them are metallo-β-lactamases which confer resistance to all β-lactams, including carbapenems.


S. aeruginosa reveals substantial resistance in the environment. It remains viable in tap water for 2.5 months, in distilled water for up to 1 year in home dust for several days. P. aeruginosa may survive even in diluted disinfectants such as quaternary ammonium compounds, as the bacterium is resistant to many antibiotics and antiseptics. However it remains sensitive to chlorine-containing biocides and 2% phenol solution. Similarly, P. aeruginosa cells easily lose their viability under routine heating or autoclaving sterilization.

Pathogenesis and Clinical Findings of P. aeruginosa Infections

Pseudomonads are widespread in nature. They are living in soil, water, and colonising plants and animals. As the external environment plays a significant role in the spread of P. aeruginosa, infections caused by these bacteria are referred to as sapronoses. Despite the presence of potent virulence factors, P. aeruginosa rarely causes infections in immunocompetent hosts. In addition, bacteria need pre-existing skin and mucosal tissue injuries for successful adherence and colonization, such as in patients with wounds, burns, trauma and other lesions. By producing ExoT toxin, P. aeruginosa inhibits cytokinesis and cell proliferation, preventing the closure of wound edges and maintaining conditions for microbial spread.

As a result, P. aeruginosa infections only develop in patients with various injuries, implanted prosthetic devices, chronic surgical diseases and tumours with impaired local and systemic immunity or after immunosuppression. These people usually stay in intensive care hospitals and surgery departments for a long time. P. aeruginosa is therefore a leading nosocomial pathogen, accounting for about 15% of all hospital-acquired infections. S. Aeruginosa colonises the tissues of the integument and penetrates the skin or mucous membranes that can initiate the spread of bacteria. The most common sources of P. aeruginosa-associated nosocomial infections are hospital microbial carriers (e.g. patients or medical staff). Major transmission routes – airborne (via contaminated aerosols) or through direct contact.

Bacteria cause a plethora of local and generalised infectious processes, including wound suppurative infections, abscesses and phlegmons with blue-green purulent discharge, osteomyelitis, otitis, meningitis, urinary tract infections. Severe disseminative infections result in sepsis with septic shock, hemorrhagic skin necrosis, spread intravascular coagulation, and adult respiratory distress. Aeruginosa is the main agent that causes so-called ventilator-associated pneumonia (VAP) – severe lung injury in patients receiving mechanical lung ventilation.

Systemic infections and VAP are characterised by high mortality rates in the range of 40-50%. A special case of P. aeruginosa infection is observed in patients with cystic fibrosis – inherited autosomal recessive disorder associated with cystic fibrosis. These patients are highly sensitive to P. aeruginosa showing a deep chronic disease with a worse prognosis. All these clinical cases are strongly aggravated by natural multidrug resistance of P. aeruginosa strains.

Laboratory Diagnosis of P. aeruginosa Infections

The specimens are obtained from wound discharge, pus, urine, blood, spinal fluid, sputum, etc. Microscopy shows single gram-negative rods. Microbial culture isolation is performed on blood agar and selective antiseptic media (cetrimide, acetamide, and others). Identification is based on the morphology of colonies with characteristic pigments, biochemical and antigenic properties. P. aeruginosa is an oxidase-positive bacterium capable of growing at 42°C. Biochemical tests, serotype determination and typing of pyocin are possible to differentiate from other pseudomonads.

Pseudomonas aeruginosa

For epidemiological purposes molecular genetic typing of P. aeruginosa isolates is conducted by various PCR-based tests.

Treatment and Prophylaxis of P. aeruginosa Infections

The treatment of infections caused by P. aeruginosa is an extremely difficult clinical condition due to the multidrug-resistant nature of these agents. In fact, they show resistance to the most effective antimicrobials (e.g. carbapenems in more than 50-60% of cases) retaining sensitivity only to members of the polymyxin group. Carbapenems are used as a standard treatment regimen in combination with respiratory fluoroquinolones (levofloxacin). Anti-pseudomonad cephalosporins (cefepime) and aminoglycosides (amikacin) may also be administered.

Multiresistant strains of P. aeruginosa are cured with polymyxin E (or colistin)-about 95% of the strains remain sensitive. Specific anti-pseudomonad immunoglobulin therapy is possible. The inactivated polyvalent pseudomonad vaccine can be used for specific immunizations with uncertain results. Specific prophylaxis is recommended for high-risk patients and for outbreaks of P. aeruginosa infection.