The Battle: Quorum-Sensing Inhibitors Versus Evolution of Bacterial Resistance
During the last few centuries, human beings had high mortality and morbidity rate. At times, a large population was completely wiped away. Although these were ‘diagnosed’ to be caused by bacterial infections, however, in the absence of any effective treatment, people helplessly watched the patient dying. The discovery of antibiotics in the twentieth century brought a revolution in human health. Microbial infections in human beings could be treated through the regular and at times indiscriminate administration of antibiotics (Davies et al. 2006). Today, bacteria have developed resistance to quite a few antibiotics (Davies and Davies 2010). Pharmaceutical companies are hesitant to invest in searching novel antibiotics. The scenario is further exacerbated by infections caused by biofilm-forming bacteria. This structure provides additional resistance to antibiotics. One needs up to 1,000 higher doses of antibiotics for dispersing the biofilm (Nadell et al. 2008). Biofilms are formed through the phenomenon known as quorum sensing (QS). QS operates through a wide range of signal molecules, the most widely reported being oligopeptides and acylhomoserine lactones (AHLs) (McDougald et al. 2007). At low cell densities bacteria continue to multiply silently and are able to evade the host’s defence (Hentzer et al. 2003). Hence, while the infection is spreading, the ‘patient’ does not realize their presence. At high cell densities, bacteria activate their arsenal of virulence, and the disease spreads so rapidly that the patient is taken by surprise. At this stage, antibiotic therapy does not function effectively. It was realized that disrupting the QS system may help to let bacteria grow without getting into virulence mode. Quite a bit of effort has gone into searching quorum-sensing inhibitors (QSIs).
KeywordsEfflux Pump Quorum Sense Quorum Sense System Acylhomoserine Lactone Quorum Sense Signal
The authors wish to thank the Director of CSIR-Institute of Genomics and Integrative Biology (IGIB), CSIR-INDEPTH (BSC0111), and the Government of India for providing the necessary funds and facilities. PK is thankful to CSIR for granting Senior Research Fellowship.
- García-Contreras R, Martinez-Vazquez M, Velazquez Guadarrama N, Villegas Paneda AG, Hashimoto T, Maeda T, Quezada H, Wood TK (2013) Resistance to the quorum-quenching compounds brominated furanone C-30 and 5-fluorouracil in Pseudomonas aeruginosa clinical isolates. Pathog Dis 68:8–11. doi: 10.1111/2049-632X.12039 PubMedCrossRefGoogle Scholar
- Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song Z, Kristoffersen P, Manefield M, Costerton JW, Molin S, Eberl L, Steinberg P, Kjelleberg S, Høiby N, Givskov M (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815. doi: 10.1093/emboj/cdg366 PubMedCrossRefPubMedCentralGoogle Scholar
- Ledgham F, Ventre I, Soscia C, Foglino M, Strugis JN, Lazdunski A (2003) Interaction of the quorum sensing regulator QscR: interaction with itself and the other regulators of Pseudomonas aeruginosa LasR and RhlR. Mol Microbiol 48:199–210. doi: 10.1046/j.1365-2958.2003.03423.x PubMedCrossRefGoogle Scholar
- Rampioni G, Schuster M, Greenberg EP, Bertani I, Grasso M, Venturi V, Zennaro E, Leoni L (2007) RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa. Mol Microbiol 66:1557–1565. doi: 10.1111/j.1365-2958.2007.06029x PubMedCrossRefGoogle Scholar
- Skindersoe ME, Zeuthen LH, Brix S, Fink LN, Lazenby J, Whittall C, Williams P, Diggle SP, Froekiaer H, Cooley M, Givskov M (2009) Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation. FEMS Immunol Med Microbiol 55:335–345. doi: 10.1111/j.1574-695X.2008.00533.x PubMedCrossRefGoogle Scholar
- Teplitski M, Robinson JB, Bauer WD (2000) Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria. Mol Plant Microbe Interact 13:637–648. doi: 10.1094/MPMI.2000.13.6.637 PubMedCrossRefGoogle Scholar