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Communication in Bactria: Quorum Sensing

Communication in Bactria: Quorum Sensing

 

Single-celled organisms, once thought capable of only performing simple tasks, are now appreciated for their ability to behave in a quorum (1, 2). Social interactions enable a group of bacteria to communicate and synchronize their collective behaviour, thereby acting like multicellular organisms. Bacteria use various means of communication among themselves and with their multicellular hosts to establish this quorum. The benefit to the bacteria is that they can achieve what they cannot do rather alone. For example, biofilm production is a result of collective behaviour that provides antibiotic resistance (1).

Cell density-dependent microbial cell-to-cell communication is known as Quorum sensing (QS). Quorum sensing is a process that allows interactions between cross-kingdom microorganisms, sharing information about cell density and adjusting gene expression accordingly (3).

Bacterial species produce and respond to small chemical signals (hormone-like) called autoinducers. When the bacterial population increases, these extracellular signaling molecules accumulate in the environment. After reaching a threshold level, these signaling molecules are sensed by specific receptors present in the surrounding population. The Signal-receptor complexes direct the expression of quorum-sensing-dependent target genes. QS system enables single-celled organisms to behave synchronously as multicellular organisms and regulates various microbial behaviours like bioluminescence, morphogenesis, pathogenesis, sporulation antibiotic production, biofilm formation, pigment production, virulence factor, and secretion secondary metabolite production (4)(5)(6).

Quorum sensing Regulation

In gram-negative organisms, QS is mediated by N-acyl-homoserine lactone (AHL) signalling molecules. The regulation of the AHL mediated QS system depends on the presence of proteins homologous to LuxI and LuxR, which were first detected controlling bioluminescence in Aliivibrio fischeri. The LuxI is a synthase that produces diffusible AHL molecule 3-oxo-hexanoyl-l-homoserine lactone (3OC6-HSL). A high density of bacterial cell population leads to increased concentrations of 3OC6-HSL, and binding to the signal receptor LuxR. The luxR receptor functions as a cytoplasmic transcriptional regulator, which binds to 3OC6-HSL and the complex regulate transcription (6). In different gram-negative species, a homologous LuxI/R system is present.

Autoinducing peptides (AIPs) participate in the Gram-positive bacterial QS system. AIP is synthesized in the ribosome as a precursor peptide, then processed and transported out of the bacterial cell. API signaling molecule binds to a sensor kinase signal receptor located in the bacterial membrane. The API/ Sensor kinase complex phosphorylates a cytoplasmic response regulator that regulates transcription of target genes (6).

Disadvantage of Quorum Sensing

Tough, QS favours bacterial survival, but it offers a negative impact for us. The greatest threat imposed by bacterial QS is the emergence of multiple drug resistance (MDR) in pathogenic species like Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhimurium (7). Many studies provide evidence that when a common drug imposes high selection pressure of “death or life” on the bacterium, it uses QS directed pathways to escape the death (7). The common ways involve biofilm production, neutralizing the drug, and pumping out the drug by using efflux pumps (7).

Since QS supervises the processes important for microbial pathogenicity, there is great interest in the concept of anti-QS therapy (also called quorum quenching) (8)

In recent years Quorum sensing mechanisms are being studied intensively in various species. Multiple pathways and chemicals involved have been characterized and Marked as a target of QS inhibition.

The use of Quorum Quenching (QQ) enzymes seems a potential way to fight against bacterial quorum sensing. Also, the administration of antibiotics along with QS inhibitors can be an approach.

Advantage of Quorum Sensing 

Bacterial social behaviour doesn’t necessarily harm us, but we get benefits from it in other ways.

The mammalian gut harbours a complex and very diverse microbial community. A healthy individual has a unique and balanced gut microbiome that helps its host maintain optimal health. An unbalanced gut microbiome consortium leads to many disorders. Various researches, suggests that QS signalling molecules present in the gut reestablish homeostasis by favouring functional gut microflora (9), protecting pathogen colonization by imposing colonization resistance, help good bacteria to get through in harsh conditions of the gastrointestinal tract.

Quorum Sensing is a process that benefits the microorganism in any given case but, in different conditions, it affects us both negatively and positively. More research in the future will find ways to benefit.

 

References:

  1. Mukherjee S, Bassler BL. Bacterial quorum sensing in complex and dynamically changing environments. Nat Rev Microbiol. 2019 Jun;17(6):371-382. doi: 10.1038/s41579-019-0186-5. PMID: 30944413; PMCID: PMC6615036.
  2. Bassler BL, Losick R. Bacterially speaking. Cell. 2006 Apr 21;125(2):237-46. doi: 10.1016/j.cell.2006.04.001. PMID: 16630813.
  3. Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, Iskandar K, Charan J, Abukabda AB, Jahan D. Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases. Expert Rev Anti Infect Ther. 2021 May;19(5):571-586. doi: 10.1080/14787210.2021.1843427. Epub 2020 Dec 8. PMID: 33131352.
  4. Padder SA, Prasad R, Shah AH. Quorum sensing: A less known mode of communication among fungi. Microbiol Res. 2018 May;210:51-58. doi: 10.1016/j.micres.2018.03.007. Epub 2018 Mar 21. PMID: 29625658.
  5. Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med. 2012 Nov 1;2(11):a012427. doi: 10.1101/cshperspect.a012427. PMID: 23125205; PMCID: PMC3543102.
  6. Azimi S, Klementiev AD, Whiteley M, Diggle SP. Bacterial Quorum Sensing During Infection. Annu Rev Microbiol. 2020 Sep 8;74:201-219. doi: 10.1146/annurev-micro-032020-093845. Epub 2020 Jul 13. PMID: 32660382.
  7. Zhao X, Yu Z, Ding T. Quorum-Sensing Regulation of Antimicrobial Resistance in Bacteria. Microorganisms. 2020 Mar 17;8(3):425. doi: 10.3390/microorganisms8030425. PMID: 32192182; PMCID: PMC7143945.
  8. Krzyżek P. Challenges and Limitations of Anti-quorum Sensing Therapies. Front Microbiol. 2019 Oct 31;10:2473. doi: 10.3389/fmicb.2019.02473. PMID: 31736912; PMCID: PMC6834643.
  9. Thompson JA, Oliveira RA, Djukovic A, Ubeda C, Xavier KB. Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota. Cell Rep. 2015 Mar 24;10(11):1861-71. doi: 10.1016/j.celrep.2015.02.049. PMID: 25801025.