Acknowledgments
L. Rodrigues was supported by the European Union’s Horizon
2020 research and innovation program under the Marie
Sklodowska-Curie grant agreement No 795924.
References
1. Du D, Wang-Kan X, Neuberger A et al (2018)
Multidrug efflux pumps: structure, function
and
regulation.
Nat
Rev
Microbiol
16:523–539
2. Pasipanodya JG, Gumbo T (2011) A new evolutionary
and
pharmacokineticpharmacodynamic scenario for rapid emergence of resistance to single and multiple antituberculosis drugs. Curr Opin Pharmacol
11:457–463
3. Piddock LJV (2019) The 2019 Garrod lecture:
MDR efflux in gram-negative bacteria-how
understanding resistance led to a new tool for
drug discovery. J Antimicrob Chemother
74:3128–3134
4. De Rossi E, Aı ´nsa JA, Riccardi G (2006) Role
of mycobacterial efflux transporters in drug
resistance: an unresolved question. FEMS
Microbiol Rev 30:36–52
5. Rodrigues L, Parish T, Balganesh M et al
(2017) Antituberculosis drugs: reducing
efflux¼increasing activity. Drug Discov Today
22:592–599
6. Adams KN, Takaki K, Connolly LE et al (2011)
Drug tolerance in replicating myco- bacteria
mediated by a macrophage-induced efflux
mechanism. Cell 145:39–53
7. Ramo ´ n-Garcı ´a S, Mick V, Dainese E et al
(2012) Functional and genetic characterization
of the tap efflux pump in Mycobacterium bovis
BCG.
Antimicrob
Agents
Chemother
56:2074–2083
8. Ramo ´ n-Garcı ´a S, Martı ´n C, Thompson CJ et al
(2009) Role of the Mycobacterium tuberculosis
P55 efflux pump in intrinsic drug resistance,
oxidative stress responses, and growth. Antimicrob Agents Chemother 53:3675–3682
9. Lee RE, Hurdle JG, Liu J et al (2014) Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug
efflux. Nat Med 20:152–158
10. Balganesh M, Dinesh N, Sharma S et al (2012)
Efflux pumps of Mycobacterium tuberculosis
play a significant role in antituberculosis activity of potential drug candidates. Antimicrob
Agents Chemother 56:2643–2651
11. Balganesh M, Kuruppath S, Marcel N et al
(2010) Rv1218c, an ABC transporter of Mycobacterium tuberculosis with implications in
drug discovery. Antimicrob Agents Chemother
54:5167–5172
12. Viveiros M, Martins M, Rodrigues L et al
(2012) Inhibitors of mycobacterial efflux
pumps as potential boosters for anti-tubercular
drugs. Expert Rev Anti-Infect Ther
10:983–998
13. Pule CM, Sampson SL, Warren RM et al
(2016) Efflux pump inhibitors: targeting
mycobacterial efflux systems to enhance TB
therapy. J Antimicrob Chemother 71:17–26
14. Greulich KO (2004) Single molecule techniques for biomedicine and pharmacology. Curr
Pharm Biotechnol 5:243–259
15. Jernaes MW, Steen HB (1994) Staining of
Escherichia coli for flow cytometry: influx and
efflux of ethidium bromide. Cytometry
17:302–309
16. Lomovskaya O, Bostian KA (2006) Practical
applications and feasibility of efflux pump inhibitors in the clinic – a vision for applied use.
Biochem Pharmacol 71:910–918
17. Blair JM, Piddock LJ (2016) How to measure
export via bacterial multidrug resistance efflux
pumps. mBio 7(4):e00840–16
18. Viveiros M, Martins A, Paixa ˜o L et al (2008)
Demonstration of intrinsic efflux activity of
Escherichia coli K-12 AG100 by an automated
ethidium bromide method. Int J Antimicrob
Agents 31:458–462
19. Ramo ´ n-Garcı ´a S, Martı ´n C, Aı ´nsa JA et al
(2006) Characterization of tetracycline resistance mediated by the efflux pump tap from
Mycobacterium fortuitum. J Antimicrob Chemother 57:252–259
20. Viveiros M, Martins M, Couto I et al (2008)
New methods for the identification of efflux
mediated MDR bacteria, genetic assessment
of regulators and efflux pump constituents,
characterization of efflux systems and screening
for inhibitors of efflux pumps. Curr Drug Targets 9:760–778
244
Liliana Rodrigues et al.
L. Rodrigues was supported by the European Union’s Horizon
2020 research and innovation program under the Marie
Sklodowska-Curie grant agreement No 795924.
References
1. Du D, Wang-Kan X, Neuberger A et al (2018)
Multidrug efflux pumps: structure, function
and
regulation.
Nat
Rev
Microbiol
16:523–539
2. Pasipanodya JG, Gumbo T (2011) A new evolutionary
and
pharmacokineticpharmacodynamic scenario for rapid emergence of resistance to single and multiple antituberculosis drugs. Curr Opin Pharmacol
11:457–463
3. Piddock LJV (2019) The 2019 Garrod lecture:
MDR efflux in gram-negative bacteria-how
understanding resistance led to a new tool for
drug discovery. J Antimicrob Chemother
74:3128–3134
4. De Rossi E, Aı ´nsa JA, Riccardi G (2006) Role
of mycobacterial efflux transporters in drug
resistance: an unresolved question. FEMS
Microbiol Rev 30:36–52
5. Rodrigues L, Parish T, Balganesh M et al
(2017) Antituberculosis drugs: reducing
efflux¼increasing activity. Drug Discov Today
22:592–599
6. Adams KN, Takaki K, Connolly LE et al (2011)
Drug tolerance in replicating myco- bacteria
mediated by a macrophage-induced efflux
mechanism. Cell 145:39–53
7. Ramo ´ n-Garcı ´a S, Mick V, Dainese E et al
(2012) Functional and genetic characterization
of the tap efflux pump in Mycobacterium bovis
BCG.
Antimicrob
Agents
Chemother
56:2074–2083
8. Ramo ´ n-Garcı ´a S, Martı ´n C, Thompson CJ et al
(2009) Role of the Mycobacterium tuberculosis
P55 efflux pump in intrinsic drug resistance,
oxidative stress responses, and growth. Antimicrob Agents Chemother 53:3675–3682
9. Lee RE, Hurdle JG, Liu J et al (2014) Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug
efflux. Nat Med 20:152–158
10. Balganesh M, Dinesh N, Sharma S et al (2012)
Efflux pumps of Mycobacterium tuberculosis
play a significant role in antituberculosis activity of potential drug candidates. Antimicrob
Agents Chemother 56:2643–2651
11. Balganesh M, Kuruppath S, Marcel N et al
(2010) Rv1218c, an ABC transporter of Mycobacterium tuberculosis with implications in
drug discovery. Antimicrob Agents Chemother
54:5167–5172
12. Viveiros M, Martins M, Rodrigues L et al
(2012) Inhibitors of mycobacterial efflux
pumps as potential boosters for anti-tubercular
drugs. Expert Rev Anti-Infect Ther
10:983–998
13. Pule CM, Sampson SL, Warren RM et al
(2016) Efflux pump inhibitors: targeting
mycobacterial efflux systems to enhance TB
therapy. J Antimicrob Chemother 71:17–26
14. Greulich KO (2004) Single molecule techniques for biomedicine and pharmacology. Curr
Pharm Biotechnol 5:243–259
15. Jernaes MW, Steen HB (1994) Staining of
Escherichia coli for flow cytometry: influx and
efflux of ethidium bromide. Cytometry
17:302–309
16. Lomovskaya O, Bostian KA (2006) Practical
applications and feasibility of efflux pump inhibitors in the clinic – a vision for applied use.
Biochem Pharmacol 71:910–918
17. Blair JM, Piddock LJ (2016) How to measure
export via bacterial multidrug resistance efflux
pumps. mBio 7(4):e00840–16
18. Viveiros M, Martins A, Paixa ˜o L et al (2008)
Demonstration of intrinsic efflux activity of
Escherichia coli K-12 AG100 by an automated
ethidium bromide method. Int J Antimicrob
Agents 31:458–462
19. Ramo ´ n-Garcı ´a S, Martı ´n C, Aı ´nsa JA et al
(2006) Characterization of tetracycline resistance mediated by the efflux pump tap from
Mycobacterium fortuitum. J Antimicrob Chemother 57:252–259
20. Viveiros M, Martins M, Couto I et al (2008)
New methods for the identification of efflux
mediated MDR bacteria, genetic assessment
of regulators and efflux pump constituents,
characterization of efflux systems and screening
for inhibitors of efflux pumps. Curr Drug Targets 9:760–778
244
Liliana Rodrigues et al.