Innovative Strategies Toward the Disassembly of the EPS Matrix in Bacterial Biofilms

Abstract

Bacterial biofilms represent a major concern at a worldwide level due to the high demand for implantable medical devices and the rising numbers of bacterial resistance. The complex structure of the extracellular polymeric substances (EPS) matrix plays a major role in this phenomenon, since it protects bacteria from antibiotics, avoiding drug penetration at bactericidal concentrations. Besides, this structure promotes bacterial cells to adopt a dormant lifestyle, becoming less susceptible to antibacterial agents. Currently, the available treatment for biofilm-related infections consists in the administration of conventional antibiotics at high doses for a long-term period. However, this treatment lacks efficiency against mature biofilms and for implant-associated biofilms it may be necessary to remove the medical device. Thus, biofilm-related infections represent an economical burden for the healthcare systems. New strategies focusing on the matrix are being highlighted as alternative therapies to eradicate biofilms. Here, we outline reported matrix disruptive agents, nanocarriers, and technologies, such as application of magnetic fields, photodynamic therapy, and ultrasounds, that have been under investigation to disrupt the EPS matrix of clinically relevant bacterial biofilms. In an ideal therapy, a synergistic effect between antibiotics and the explored innovated strategies is aimed to completely eradicate biofilms and avoid antimicrobial resistance phenomena.

The Role of Bacterial Biofilm in Antibiotic Resistance and Food Contamination

“…The antibiotic resistance used by bacteria in biofilm is distinct and different from natural or innate resistance mechanisms [ 48 ] ( Figure 2 ). 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 [ 38 ] ( Figure 2 ). 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 [ 34 , 83 ].…”

“…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 [ 75 – 77 ]. The extracellular polymeric substances (EPS) matrix protects bacteria from antibiotics, avoiding drug penetration at bactericidal concentrations [ 38 ] (Figures 1 and 2 ). Bacteria within a biofilm are several orders of magnitude more resistant to antibiotics, compared with planktonic bacteria [ 78 ].…”

“…Thus, this multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials [ 37 ]. To sum up, bacterial biofilm is a key player in the development of antimicrobial resistance [ 38 ].…”

“…Biofilm formation is the main virulence factor for a wide range of microorganisms that cause chronic infections [37]. Bacterial biofilm represents a major health concern due to the high demand for implantable medical devices and the rising numbers of bacterial resistance [38]. Pathogenic microorganisms can produce biofilm on implanted devices [39].…”

Synergistic effects of D-arginine, D-methionine and D-histidine on the inhibition and eradication of Porphyromonas gingivalis biofilm

“…Therefore, strategies focusing on disruption of the EPS matrix have attracted much attentions recent years, which may increase bacterial susceptibility to antibacterial agents. Due to the characteristics of EPS matrix, those strategies can be classi ed into matrix disruptive agents, nanocarriers and bio lm physical removal technologies (magnetic eld, photodynamic therapy, ultrasounds) 8 . But they usually have common disadvantages, such as low bioavailability at later stage 9 or less effective during eradicating mature bacterial bio lms 10 .…”