Table 1.

Studies reporting microbial interactions with P. aeruginosa.

Sp Interacting with PA	Microbial/Host Response	Potential Implications on Disease	Ref(s).
Gram-positives	↑ lytic activity by PA ↓ Gram+ in vivo models	PA more toxic in co-infections with Gram+	[114]
	↑ pyocyanin production by PA	PA mechanisms of dominance	[115]
S. aureus	Co-infection strains less competitive than mono-infection strains	Adaptation to coexistence in the lung	[116]
	PA induces bronchial epithelial cells to produce phospholipase, sPLA2-IIA	Manipulation of host immune response, enhanced survival of PA, and killing of SA and other Gram+	[117]
	PA EPS can affect mixed species biofilm architecture	Proximity of SA and PA in mixed biofilms	[118]
	↑ PA siderophore production Lysis of SA	Iron competition LasA protease	[112] [119,120]
	PA LPS inactivation mutations ↓ production of PA LPS in anoxia	Reduced recognition by immune system, persistence Immune evasion	[112] [112]
	↑ PA swimming motility in anoxia	Reseeding of infection in lung	[17]
S. maltophilia	Co-colonise the CF airway	Opportunity to interact	[121]
	↓ SM growth ↑ PA biofilm	Altered virulence and persistence	[18] [111]
	↓ Adhesion of PA to CFBE	Evasion of immune system and persistence	[18]
Streptococci spp.	↓ SMG growth—PA competition for iron ↓ S. anginosus growth and biofilm formation ↑ Strep spp. biofilm formation—hijacks PA EPS ↓ PA viability—Strep H2O2 production	Pathogen dominance and persistence Altered virulence and persistence Persistence Strep beneficial to host	[122] [123] [124,125] [126]
Burkholderia cepacia complex	↓ PA virulence factors	Altered virulence	[127]
	PA enhances Bcc virulence	Altered virulence	[128]
	↓ PA growth in vivo	Altered persistence	[129]
	Reduced growth of Bcc and PA	Competition beneficial to host?	[130]
	Co-infection ↑ inflammatory markers	Increased host inflammation	[19]
A. fumigatus	Co-colonise the CF airway	Opportunity to interact in airway	[131]
	Co-colonised patients—↓ lung function, ↑ hospitalisations, exacerbations and Abx usage	Poorer disease outcome	[16]
	PA SNs stimulate AF growth	Increased AF abundance in co-infections *	[131]
	Metacaspases from Pa SNs inhibit and damage AF biofilms	Reduced AF abundance in co-infections	[132]
	↑ elastase production by PA in presence of AF	More damaging pathology	[133]
	SNs from co-cultures more toxic to epithelial cells lines	More damaging pathology	[133]
	Mutually antagonistic	Competition beneficial to host?	[134]
	Gliotoxin produced by AF reduces PA biofilm	Competition beneficial to host?	[134]
	Co-infections cause altered inflammatory response	Evasion of the immune system and persistence	[134]
	PA dirhamnolipids induce AF ECM production	Inhibits AF growth and facilitates PA binding	[135]
	PA phenazines inhibit AF growth by direct contact	Reduced AF abundance in co-infections	[136]
	Subinhibitory concentrations of PA phenazines can promote AF growth	Increased AF abundance in co-infections *	[136]
	Iron competition	Reduced AF abundance in co-infections	[137,138]
	Development of PA SCVs	Reduced AF abundance in co-infections	[139]
	Expression of QS molecules	Reduced AF abundance in co-infections	[135,140,141,142]
C. albicans	PA expressed LPS inhibits CA biofilm formation and hyphal development	Reduced CA abundance and virulence in co-infections	[143]
	PA QS molecule, 3-oxo-C12HSL	Reduced CA abundance in co-infections	[144]
	PA 2-heptyl-3-hydroxyl-4-quinolone	Reduced CA abundance in co-infections	[145]
	CA secreted Farnesol reduces PA pyocyanin Farnesol inhibits PA haemolysin Farnesol inhibits PA swarming motility	PA less virulent	[146]
		PA less virulent	[147]
		PA less virulent	[144]
	CA secreted tyrosol inhibits PA haemolysin and protease production	PA less virulent	[147]

PA = P. aeruginosa, SA = S. aureus, SM = S. maltophilia, AF = A. fumigatus, CA = C. albicans, Bcc = Burkholderia cepacia complex, SMG = Streptococcus milleri group, SNs = supernatants, EPS = exopolysaccharide, LPS = lipopolysaccharide, CFBE = cystic fibrosis bronchial epithelial cells, ECM = extracellular matrix, Abx = antibiotics, QS = quorum sensing, SCVs = small colony variants. * contradictory findings.