DISCOVERIES 2019, Jul-Sep, 7(3): e100 DOI: 10.15190/d.2019.13 Bacteria and biofilm formation REVIEW Article Communication is the key: biofilms, quorum sensing, formation and prevention Veronica Georgiana Preda1,2,*, Oana Săndulescu3,* 1Department of Biochemistry and Molecular Biology, University of Bucharest, Faculty of Biology, Bucharest, Romania; 2Department of Genetics and Applied Biotechnology, University of Bucharest, Faculty of Biology, Bucharest, Romania; 3Department of Infectious Diseases I, Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest, Romania. * Corresponding authors: Veronica Georgiana Preda, Department of Biochemistry and Molecular Biology, University of Bucharest, Faculty of Biology, 1-3 Intrarea Portocalelor, Bucharest, Romania; E-mail: [email protected]; Oana Săndulescu, MD, PhD, Department of Infectious Diseases I, Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania. E-mail: [email protected] Submitted: Sept. 24th, 2019; Revised: Sept. 29th, 2019; Accepted: Sept. 29th, 2019; Published: Sept. 30th, 2019; Citation: Preda VG, Săndulescu O. Communication is the key: biofilms, quorum sensing, formation and prevention. Discoveries 2019, 7(3); e100. DOI:10.15190/d.2019.13 ABSTRACT Keywords: Antibiotic resistance is a relevant topic nowadays, Biofilm formation, Staphylococcus aureus, representing one of the main causes of infection- Pseudomonas aeruginosa, quorum sensing, biofilm related mortality and morbidity at a global level. prevention. This phenomenon is worrisome and represents an area of interest for both clinical practice and SUMMARY fundamental research. One important mechanism 1. Introduction whereby bacteria acquire resistance to antibiotics 2. Biofilm-producing bacteria and evade the immune system is by forming 2.1 Staphylococcus aureus biofilms. It is estimated that ~80% of the bacteria 2.2 Pseudomonas aeruginosa producing chronic infections can form biofilms. 2.3 Other bacteria During the process of biofilm formation 3. Biofilm development, quorum sensing and quorum microorganisms have the ability to communicate quenching with each other through quorum sensing. Quorum 4. Prevention of biofilm formation sensing regulates the metabolic activity of 5. Limitations and challenges planktonic cells, and it can induce microbial biofilm 6. Conclusion formation and increased virulence. In this review we Abbreviations describe the biofilm formation process, quorum sensing, quorum quenching, several key infectious National Institute of Health (NIH); soluble microbial bacteria producing biofilm, methods of prevention products (SMPs); Extracellular polymeric substances and their challenges and limitations. Although (EPS); Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK); extremely-drug resistant progress has been made in the prevention and (XDR); methiciling-resistant Staphylococcus aureus; treatment of biofilm-driven infections, new quorum sensing (QS); Minimum Information About a strategies are required and have to be further Biofilm Experiment (MIABiE); environmental DNA developed. (eDNA). www.discoveriesjournals.org/discoveries 1 Bacteria and biofilm formation 1. Introduction the biofilm and the biofilm-producing bacteria can alter the food quality and compromise food safety. Bacterial biofilm is produced by ~80% of bacteria The biofilm can be found inside food recipients such responsible for chronic infections and it is an as vats, mixing tanks or utensils used in food important virulence mechanism, inducing resistance preparation9. to antimicrobials and evasion from the host’s Current biofilm control strategies employed in immune system1. The bacteria producing biofilm both hospitals and food industry (e.g., cleaning, comprise a diverse group of organisms, including disinfection, surface preconditioning) are efficient to both Gram-negative and Gram-positive bacteria, some extent. However, they are still far from the aerobic and anaerobic, motile and non-motile, just to desired effect and control4, and biofilm-driven name a few. infections commonly recur. New strategies for Biofilm has a remarkable complexity and three- targeting biofilms are thus required. One such dimensional organization2 and forms when biofilm- strategy is the targeting of the quorum sensing producing bacteria in an aqueous environment system, which disrupts cell-to-cell communication, adhere to solid surfaces and produce a network of conjugation, nutrient acquisition and even motility extracellular polymeric substances (EPS), adopting a and production of certain metabolites4. “multicellular lifestyle”3. These substances include but are not limited to: proteins, polysaccharides, 2. Biofilm-producing bacteria and infections lipids, DNA and form a protective matrix around bacteria, supporting their integrity and survival4. The Based on the National Institute of Health (NIH)’s microorganisms occupy about 10-30% of the biofilm statistics, biofilm formation is present in about 65% volume. Approximately 97% of the biofilm is water, of all bacterial infections and approximately 80% of which is responsible for the flow of nutrients all chronic infections (Table 1)30,31. Evaluation of required for bacterial survival within the biofilms5,6. the device-related infections resulted in several Some types of microorganisms first form aggregates estimates, including 40% for ventricular-assist of planktonic/free cells in an aqueous environment, devices, 2% for joint prostheses, 4% for mechanical as a first step inbiofilm formation7. heart valves and 6% for ventricular shunts. Biofilm is a useful adaptation of micro- Moreover, bacterial colonization of the indwelling organisms, enabling them to survive in certain devices was associated with infections in 4% of the environments4. Generally, microorganisms inside the cases when pacemakers and defibrillators were biofilm are more difficult to eradicate than when utilized, but also in 2% of breast implant cases32. present as single cells. This resilience is primarily Infective valve endocarditis is an infection of due to the tolerance mediated by the biofilm-related the heart which usually occurs as the result of the extracellular network, metabolic dormancy and other adherence of bacteria to the endothelium. The most potential mechanisms. Genetic factors do not play a common germs involved in infective endocarditis major role in this type of resistance, although the are staphylococci and streptococci, members of the close proximity of the cells may also facilitate the HACEK group, Gram-negative bacteria but fungal transfer of resistance genes8. strains have also been described33. Seeding of the Both Gram-positive bacteria, such as endothelium generally occurs from colonization or Staphylococcus aureus and Gram-negative bacteria, infection of different tracts, for example the such as Pseudomonas aeruginosa can be very genitourinary and gastrointestinal tract34, or through difficult to eradicate when forming biofilms. Biofilm direct crossing of the skin barrier either due to formation has significant implications and it is a wounds or through injecting drug use. serious problem in a few different fields, including Other types of biofilm-driven infections include healthcare/clinical care and food industry. In the chronic wounds, diabetic foot infections, or hospital setting, there are specific bacteria, including pulmonary infections in patients with cystic fibrosis, Staphylococcus epidermidis, Pseudomonas to name only a few. aeruginosa and many others which colonize tissue from patients with chronic diseases, implants and/or 2.1 Staphylococcus aureus catheters4. Most device-associated infections are due Staphylococcus aureus is a Gram-positive coccus to microbial biofilm formation. In the food industry, that causes infections in certain conditions and is www.discoveriesjournals.org/discoveries 2 Bacteria and biofilm formation Table 1. Examples of bacterial species involved in biofilm formation and their biological effects Bacterial strain Gram stain Types of infections Reference Staphylococcus Gram-positive Chronic biofilm infections, right valve 10,11,12 aureus endocarditis, chronic wound infection, lung infections in patients with cystic fibrosis Staphylococcus Gram-positive Endocarditis, catheter-related infection, joint 13,14,15 epidermidis prosthesis infection Streptococcus Gram-positive Lung infections, bacterial meningitis, acute or 16 pneumoniae chronic otitis media Listeria Gram-positive Co-culture interactions with Pseudomonas, 17,18 monocytogenes Vibrio strains, listeriosis, contamination of food products Burkholderia Gram-negative Opportunistic infections in patients with blood 19 cepacia cancer Escherichia coli Gram-negative Hemolytic uremic syndrome, acute diarrheic 20 syndrome, urinary tract infections Klebsiella Gram-negative Bacteremia, liver abscess, urinary tract 21 pneumoniae infections Pseudomonas Gram-negative Urinary tract infection 22, 23 putida Pseudomonas Gram-negative Osteomyelitis, ventilator-associated pneumonia, 10 aeruginosa lung infections in patients with cystic fibrosis, opportunistic infections in neutropenic patients, nosocomial infections Pseudomonas Gram-negative Bioremediation, biocontrol- Pythium, Fusarium, 17,24,25,26 fluorescens antimicrobial properties – production of mupirocin Rhizobium Gram-negative Biocontrol properties