. Author manuscript; available in PMC: 2023 Mar 1.

Published in final edited form as: Nat Rev Microbiol. 2021 Sep 16;20(3):129–142. doi: 10.1038/s41579-021-00620-w

Table 1.

Secondary metabolites produced by opportunistic or enteric pathogens and their impacts on antibiotic efficacy.

Metabolite	Producer	Antibiotic affected	Mechanism	Refs
PYO	Pseudomonas aeruginosa	Fluoroquinolones, aminoglycosides^*, chloramphenicol, carbenicillin	Efflux induction, oxidative stress response induction	^36,44,45
PCA, PCN	P. aeruginosa	Ciprofloxacin, tobramycin, carbenicillin	Metabolic changes	⁴⁴
Paerucumarin	P. aeruginosa	Chloramphenicol, ciprofloxacin	Efflux induction	⁵⁰
Indole	Escherichia coli	Fluoroquinolones, gentamicin, ampicillin, carbenicillin	Efflux induction, oxidative stress response induction	^27,31,77,111
Salicylate	Burkholderia spp.	Chloramphenicol, trimethoprim, ciprofloxacin	Efflux induction	⁵⁵
HQNO	P. aeruginosa	Meropenem	Increased extracellular DNA release and biofilm formation	¹⁵³
Ergothioneine	Mycobacterium tuberculosis	Rifampicin, isoniazid, bedaquiline, clofazimine	Direct ROS detoxification, redox buffering	⁸⁹
Polyamines (putrescine, spermidine)	E. coli, Burkholderia cenocepacia, P. aeruginosa	Levofloxacin, amikacin, cefotaxime, polymyxin B, norfloxacin, rifampicin, tobramycin	Direct ROS detoxification, decreased drug penetration	^99,101
PQS	P. aeruginosa	Ciprofloxacin, oxofloxacin, imipenem, meropenem, gentamicin, colistin	Increased ROS generation	^103,105
H₂S	Diverse microorganisms	Gentamicin, amikacin, nalidixic acid, ciprofloxacin, ampicillin	Oxidative stress response induction, Fe²⁺ sequestration, redox buffering	^97,154
Staphyloxanthin	Staphylococcus aureus	ND	Direct ROS detoxification	^90,91
Carotenoids	Streptococcus spp.	ND	Direct ROS detoxification	^92,93
2,3-dihydroxybenzoate	E. coli	ND	Efflux induction	²⁵
Toxoflavin	Burkholderia spp.	ND	Efflux induction^, oxidative stress response induction^	^65,68
Phthiocol	M. tuberculosis	ND	Oxidative stress response induction^**	^155,156
D-alanylgriseoluteic acid	Pantoea agglomerans	ND	Oxidative stress response induction^**	^157,158
β−3H-indolydenopyruvate	Achromobacter sp.	ND	ND	¹⁵⁹
Anthraquinones (for example, emodin, endocrocin)	Aspergillus spp.	ND	ND	^160,161

HQNO, 2-n-heptyl-4-hydroxyquinoline N oxide; PCA, phenazine 1-carboxylic acid; PCN, phenazine 1-carboxamide; PQS, Pseudomonas quinolone signal; PYO, pyocyanin, ROS, reactive oxygen species.

ND, not determined; these are molecules whose effects on antibiotics have not been directly tested.

For aminoglycosides, PYO has been shown to increase or decrease antibiotic resilience, depending on the studied conditions.

^**

Hypothesized mechanisms by which the molecule might affect susceptibility.