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. 2021 Apr 28;121(9):5479–5596. doi: 10.1021/acs.chemrev.1c00055

Table 1. List of Characterized Tripartite Systems in Gram-Negative Bacteria and Their Substrate Profilesa.

Microorganism Efflux pump family Efflux system Substrates refs
Acinetobacter baumannii RND AdeABC AG, BL, CHL, CHX, ML, FA, FQ, TET, TGC, TMP (11, 19, 20)
    AdeFGH CHL, FQ, SUL, TET, TGC, TMP (21)
    AdeIJK BL, CHL, CHX, ERY, FA, FQ, NOV, TET, TGC, TMP, TRI (11)
    AbuO AG, BL, TGC (22)
    ArpAB AG (23)
  ABC MacAB-TolC ML (24)
Acinetobacter Genomic DNA Group 3 RND AdeDE CHL, FQ, TET (25, 26)
    AdeXYZ CHL, FQ, BL, TET (25)
Achromobacter spp. RND AxyXY-OprZ AG, FQ (27)
    NccABC Cd2+, Co2+, Ni2+ (28)
Aeromonas hydrophila RND AheABC RIF (29)
Aggregatibacter actinomycetemcomitans ABC LtxDB-TolC LTX (30)
Bacteroides fragilis RND BmeABC3 BL, FQ (31)
Borrelia burgdorferi RND BesABC ML (32)
Bordetella pertussis ABC CyaBDE ACT (33)
Bradyrhizobium japonicum RND BdeAB-? AG (34)
Brucella suis RND BepDE-BepC ACR, AMP, DOC, EB, FQ, NOV, PMB, SDS, TET (35)
    BepFG-BepC DOC, NAL, SDS (35)
Burkholderia cenocepacia RND CeoAB-OpcM CHL, FQ (36)
    BCAL2820-BCAL2822 ATM, AG, CHL, FQ (37)
Burkholderia pseudomallei RND AmrAB-OprA AG, ML (38)
    BpeAB-OprB AG, CHL, ML, TET (38, 39)
    BpeEF-OprC CHL, TET, TMP (40)
Burkholderia thailandensis RND AmrAB-OprA AG, ML, TET (41)
Campylobacter jejuni RND CmeABC CHL, CTX, ML, FA, FQ, TRI (42, 43)
    CmeDEF CTX, FQ, TRI (44)
Caulobacter crescentus RND NczABC Co2+, Cd2+, Ni2+, Zn2+ (45)
Cupriavidus metallidurans RND ZneCAB Zn2+ (46)
Dickeya zeae RND DesABC ZMN (47)
Enterobacteriaceaeb RND AcrAB-TolC ACR, BAC, BL, CHL, EB, ERY, FA, FQ, NOV, OXN, TET, TGC, TRI, RIF, R6G (10, 4850, 52)
    OqxAB-TolCc CHL, FQ, ML, NIT, TGC (53)
Escherichia coli RND AcrAD-TolC AG, BL (54, 55)
    AcrEF-TolC ACR, BL, CHL, FQs, EB, ERY, R6G, TET, TGC (10, 56, 57)
    MdtEF-TolC BL, BAC, ML, OXN (10, 5658)
    CusABC Ag+, Cu+ (59)
  ABC MacAB-TolC ML (60)
    HlyBD-TolC AH (61)
    YhbFGSR- EB, TET (62)
    TolC MJ25 (63)
    YojI?-TolC    
  MFS EmrAB-TolC FQ, NOV, TRI (10, 56)
    EmrKY-TolC TET (64)
    MdtNOP ACR, PUR (56)
    AaeAB-? pHBA (65)
Helicobacter pylori RND HefABC AG, BL, CHL, EB, ERY, FQ, NOV, TET (66)
    HefDEF Cd2+, Ni2+, Zn2+ (67)
Klebsiella aerogenes RND EefABC CHL, BL, ERY, FQ (68)
Klebsiella pneumoniae RND AcrAB BAC, BL, ML, FQ, TET, NOV (69, 70)
    EefABC BAC, BL, FQ, ERY, TET, NOV (70)
    KexEF BL, ERY, TET, NOV (70)
    KexD ML (71)
    KexVWX BL, NOV  
    TMexCXD1-TOprJ1c AG, FQ, TGC (72)
  MFS KpnGH-TolC BL, AG, ML (73)
Legionella pneumophila RND LpeAB ML (74)
Moraxella catarrhalis RND AcrAB-OprM CTX, ML (75)
Neisseria gonorrhoeae RND MtrCDE BL, BS, FQ, ML, TET (76, 77)
  ABC MacAB-MtrE ML (78)
  MFS FarAB-MtrE FA (79)
Porphyromonas gingivalis RND XepCAB RIF (80)
Pseudomonas aeruginosa RND MexAB-OprM AG, BL, CHL, COL, EB, FQ, ML, SDS, SUL, TET, TMP, TRI (12, 81)
    MexCD-OprJ BL, CHL, CHX, COL, FQ, ML, QAC, TET, TGC, TMP, TRI (81)
    MexEF-OprN CHL, FQ, TET, TMP, TRI (82)
    MexGHI-OpmD ACR, EB, FQ, TET (83)
    MexJK-OprM/OpmH ERY, TET, TRI (84)
    MexMN-OprM CHL (85)
    MexPQ-OpmE ML, FQ (85)
    MexVW-OprM ACR, CHL, EB, ERY, FQ, TET (86)
    MexXY-OprA/OprM AG, BL, CHL, FQ, ML, TET, TGC (81)
    MuxABC-OpmB ATM, ERY, FQ, NOV, TET (87)
    TriABC-OpmH TRI (88)
Pseudomonas putida RND ArpABC BL, CHL, ERY, TET (89)
    MepABC BL, ERY, TET (90)
    ParXY/TtgC AG, FQ (91)
    SrpABC OS (92)
    TtgABC BL, CHL, ERY, OS, TET (93)
    TtgDEF OS (94)
    TtgGHI OS (95)
Pseudomonas fluorescens RND EmhABC CHL (96)
Pseudomonas syringae RND PseABC ACR, ERY, TET (97)
Riemerella anatipestifer RND RaeABC AG, SDS (98)
    RaeEF-RopN AG, SDS (99)
Salmonella enterica RND AcrAD-TolC ATM, BL, NOV, SDS (100)
    AcrEF-TolC ACR, BAC, BL, CHL, EB, FUS, FQs, NOV, R6G, SDS, TET, TRI (101)
    MdtABC-TolC NOV (101)
    MdsABC Au3+, BAC, BL, CHL, NOV (102)
    SilABCc Ag+ (103)
  ABC MacAB-TolC ML (101)
  MFS EmrAB-TolC NAL, NOV, TRI (101)
Serratia marcescens RND SdeAB CHL, FQ, QAC (104)
    SdeGH FQ (105)
    SdePQ FQ (105)
    SdeXY-HasF BAC, CHL, CHX, FQ, ML, QAC, TET, TGC, TRI (106, 107)
Sinorhizobium meliloti RND SmeAB-TolC ACR, CHL, ERY, NAL, RIF, SDS, TET (108)
    SmeCD-TolC CHL, NAL (108)
    SmeEF-TolC ERY, TET (108)
Stenotrophomonas maltophilia RND SmeABC AG, BL, FQ (109)
    SmeDEF CHL, FQ, ML, TET, TRI (110)
    SmeGH BL, CHL, FQ, ML, TET (109, 111)
    SmeIJK AG, TET (109)
    SmeOP-TolC AG, FQ, ML, TET (112)
    SmeVWX CHL, FQ, TET (113)
    SmeYZ AG, TET (114)
  MFS EmrCAB CCCP, NAL (115)
  ABC MacABC AG, ML, PMB (116)
    FuaABC FUA (117)
    SmaAB AMK (118)
    SmaCDEF LEV (118)
Vibrio cholerae RND VexAB- TolC AMP, ERY, NOV, PEN, PMB, SDS (119, 120)
    VexCD-TolC BS, DTG, ERY (119)
    VexEF- TolC BAC, DOC, EB, ERY, NOR, NOV, SDS, TET, TMP (119)
    VexGH DTG, NOV (121)
    VexIJK BS, DTG (120)
  MFS VceCAB CCCP, DOC, NAL (122)
Vibrio parahaemolyticus RND VmeAB-VpoC ACR, BL, BS, EB, FQ, ML, NOV, R6G, SDS, TET, TMP (123)
    VmeCD-VpoC BAC, BL, BS, ML, NOV, R6G, SDS (124)
    VmeEF-VpoC BC, EB, NOV, R6G, SDS (124)
    VmeGHI-VpoC SDS (124)
    VmeTUV-VpoC ACR, BL, BAC, BC, CHX, EB, R6G, SDS (124)
    VmeYZ-VpoC BC, NOV, SDS (124)
a

ABC, ATP-binding cassette; ACR, acriflavine; ACT, adenylate cyclase toxin; AG, aminoglycosides; AH, α-hemolysin; AMK, amikacin; AMP, ampicillin; ATM, aztreonam; BAC, benzalkonium chloride; BL, β-lactams; BS, bile salts; CCCP, carbonyl cyanide m-chlorophenylhydrazone; CHL, chloramphenicol; CHX, chlorhexidine; COL, colistin; CTX, cefotaxime; DOC, deoxycholate; DTG, detergents; ERY, erythromycin; EB, ethidium bromide; FA, fatty acids; FUS, fusidic acid; FQ, fluoroquinolones; FUA, fusaric acid; LEV, levofloxacin; LTX, leukotoxin; MFS, major facilitator superfamily; MJ25, microcin J25; ML, macrolides; NAL, nalidixic acid; NIT, nitrofurantoin; NOR, norfloxacin; NOV, novobiocin; OS, organic solvents; OXN, oxazolidinones; PEN, penicillin; pHBA, p-hydroxybenzoic acid; PMB, polymyxin B; PUR, puromycin; QAC, quaternary ammonium compounds; R6G, rhodamine 6G; RIF, rifampicin; RND, resistance-nodulation-division; SDS, sodium dodecyl sulfate; SUL, sulfonamides; TET, tetracycline; TGC, tigecycline; TMP, trimethoprim; TRI, triclosan; ZMN, zeamines.

b

A large family of Gram-negative bacteria that includes several important pathogenic species such as Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, and Shigella flexneri.

c

Pumps that are encoded in plasmids.