Antibiotic Resistance and Bacterial Biofilm: Causes and Threats
What are antibiotics?
Antibiotics are medicines used to treat or prevent infections caused by any of the following organism Bacteria Virus Fungi Parasite Protozoa Yeast Molds, etc.
What is antibiotic resistance?
Antibiotic resistance (AR) is the ability of organisms (bacteria, virus, yeast, fungi, parasites) to nullify the effect of antimicrobial drugs resulting in these drugs becoming ineffective. Antibiotic resistance happens when organisms like bacteria, virus, yeast, parasites and fungi develop the ability to defeat the drugs designed to kill them. Microorganisms that develop antimicrobial resistance are sometimes referred to as “superbugs”. Antibiotic resistant organisms are free to grow, multiply and cause infection within the host even when exposed to antibiotics. Antibiotic resistance is a major obstacle in the treatment of infectious diseases caused by bacteria. Resistance to antimicrobial agents has become a major source of threat, morbidity and mortality worldwide(1)(2). Typical resistance mechanism against antibiotics
Antibiotic resistance happens when bacteria change and become resistant to the antibiotics used to treat the infections they cause. Over-prescribing of antibiotics Patients not finishing their treatment Over-use of antibiotics in livestock and fish farming Poor infection control in hospitals and clinics Lack of hygiene and poor sanitation Lack of new antibiotics being developed
Antibiotic Resistance in Bacterial Biofilms
What is Biofilm? A biofilm is composed of living, reproducing microorganisms, such as bacteria, that exist as a colony, or community. In other words, biofilms are alive and have a complex social structure that scientists and engineers are still trying to unravel, a structure that both protects them and allows them to grow. A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface that provide protection for bacteria and make them more suitable for the external environment under certain conditions. Biofilms are populations of bacteria that adhere to surfaces and exist as organized structures which are held together in a liquid matrix that provides stability and structural integrity. When bacteria grow as biofilms, they become resistant to antibiotics and other agents that would generally have a bacteriostatic or bactericidal effect. Bacteria can proliferate either as independent cells singularly or in organized aggregates as biofilms(3)(4). Antibiotic resistance and biofilm tolerance are naturally and inextricably linked, and together create a formidable threat and catalyst in chronic infections The formation of biofilms is found to be one of the leading causes of antimicrobial resistance. Early research revealed that bacterial biofilms exist as clusters in a liquid matrix composed of proteins, polysaccharides, and extracellular DNA (cDNA), which constitute the extracellular polymeric substances. Biofilm formation is considered the core reason why antimicrobial treatment fails, and it is estimated that about 65–80% of all infections are biofilm-related; this presents a grim trial. These biofilms are the reason for certain chronic infections being more common in cystic fibrosis and delayed wound healing and are often associated with medical instruments such as heart valves, prostheses, catheters, implants, contact lenses, pacemakers, and ventricular assist devices. Several species of bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa are implicated as the cause of many chronic infections, due to their resistance to antibiotics and the formation of biofilms(5).
Fundamental Basis for Bacterial Biofilm Formation
Bacteria form biofilms in response to environmental stresses such as UV radiation, desiccation, limited nutrients, extreme pH, extreme temperature, high salt concentrations, high pressure, and antimicrobial agents. Why form bacterial biofilm? Reasons behind the formation of bacterial biofilm Given below some potential incentives behind the formation of biofilms by bacteria during infection are considered: Resists phagocytosis by protozoa and immune cells Collect nutrients from flowing liquid Nutrient exchange Resists penetration of drug (e.g. antibiotics), this leads to antibiotic resistance Genetic exchange Protection from harmful conditions in the host (defense) Sequestration to a nutrient-rich area (colonization) Utilization of cooperative benefits (community)
Threats of Bacterial biofilm
Bacterial biofilm is important concern in Healthcare issues, Plant diseases, Food safety and the Food industry, Drinking Water Distribution Systems, Marine Biofouling etc. Bacterial biofilm formation, a threat to health issues and its Impact on Antibiotic Resistance: The emergence and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. Antibiotic resistance is one of the consequences of the bacterial biofilm communities which contribute to chronic infections. Biofilm is recalcitrant to antibiotic therapy and a major cause of persistent and recurrent infections by clinically important pathogens worldwide. This is because the formation of biofilms and subsequent encasement of bacterial cells in a complex matrix can enhance resistance to antimicrobials and sterilizing agents making these organisms difficult to eradicate and control(4). The extracellular polymeric substances (EPS) matrix protects bacteria from antibiotics, avoiding drug penetration at bactericidal concentrations. Bacteria within a biofilm are several orders of magnitude more resistant to antibiotics, compared with planktonic bacteria. For instance, biofilms can tolerate antimicrobial agents at concentrations of 10–1000 times that needed to inactivate genetically equivalent planktonic bacteria. The nature of biofilm structure and other physiological changes such as slow growth rate assists them to be resistant to antimicrobial agents. Microorganisms in a biofilm are resistant due to the following suggested factors(6):
Polymeric matrix that can restrict diffusion of antibiotics
Interaction of antibiotics with a polymeric matrix which lowers their activity
Enzyme-mediated resistance such as β-lactamase
Changes in metabolic activity inside the biofilm
Genetic changes on target cells or hiding the target sites
Extrusion of antibiotics using efflux pumps
The presence of outer membrane structure such as in Gram-negative bacteria
These mechanisms are critical for antibiotic resistance and survival of biofilm bacteria. The antibiotic resistance used by bacteria in biofilm is distinct and different from natural or innate resistance mechanisms. As similar findings revealed bacteria within biofilm develop different molecular strategies to protect their cells from hostile conditions such as the interaction of biofilm matrix with antibiotics that can retard or lower their activities, slow growth rates in which antibiotics will not be effective, genetic related resistance, and producing persistent cells which are tolerant to different antibiotics. In biofilm-forming bacteria, there is a high rate of mutation that enables them to develop resistant mechanisms, and this, in turn, gives an opportunity for their genes to produce enzymes that inactivate the antibiotics or expel the antibiotics using efflux pumps. Bacteria within biofilm produce persister cells that are metabolically inert and it is one of their mechanisms to escape from antibiotics and even they have the ability to survive in high concentration of antibiotics. Biofilm plays a critical role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. The number of microorganisms within the matrix is too dense so that there is close contact between different microorganisms which enable them to exchange resistant genes and finally, the whole community may acquire that resistant gene. Therefore, genetic diversification of microorganisms in biofilm is largely responsible for shaping antibiotic resistance. As studies have suggested that biofilm is important for the transfer of conjugative plasmids due to the high proximity of cells within this multicellular structure. The resistance of biofilm to antibiotics depends on different factors such as physical, physiological, and gene-related factors. Thus, this multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials(4)(5). To sum up, bacterial biofilm is a key player in the development of antimicrobial resistance and leads to cause disease of different body system (Table-1) References: 1. Yelin I, Kishony R. Antibiotic Resistance. Cell [Internet]. 2018;172(5):1136-1136.e1. Available from: http://dx.doi.org/10.1016/j.cell.2018.02.018 2. Frieri M, Kumar K, Boutin A. Antibiotic resistance. J Infect Public Health [Internet]. 2017;10(4):369–78. Available from: http://dx.doi.org/10.1016/j.jiph.2016.08.007 3. Eze EC, El Zowalaty ME, Pillay M. Antibiotic resistance and biofilm formation of Acinetobacter baumannii isolated from high-risk effluent water in tertiary hospitals in South Africa. J Glob Antimicrob Resist [Internet]. 2021;27:82–90. Available from: https://doi.org/10.1016/j.jgar.2021.08.004 4. Joseph HA, Swamy SS, Solomon AP. Antibiotic Resistance in Biofilms. ACS Symp Ser. 2019;1323:205–24. 5. Bowler PG. Antibiotic resistance and biofilm tolerance: A combined threat in the treatment of chronic infections. J Wound Care. 2018;27(5):273–7. 6. Antimicrobial resistance : a global threat. Essent Drugs Monit. 2000;(28 & 29):36.