The ability to fight bacterial infections with antibiotics has been a longstanding cornerstone of modern medicine. However, wide-spread overuse and misuse of antibiotics has led to unintended consequences, which in turn require large-scale changes of policy for mitigation. In this review, we address two broad classes of corollaries of antibiotics overuse and misuse. Firstly, we discuss the spread of antibiotic resistance from hotspots of resistance evolution to the environment, with special concerns given to potential vectors of resistance transmission. Secondly, we outline the effects of antibiotic pollution independent of resistance evolution on natural microbial populations, as well as invertebrates and vertebrates. We close with an overview of current regional policies tasked with curbing the effects of antibiotics pollution and outline areas in which such policies are still under development.

https://www.mdpi.com/2076-2607/7/6/180/pdf

Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy

Metal‐Based Nanomaterials in Biomedical Applications: Antimicrobial Activity and Cytotoxicity Aspects

Bacterial biofilms are complex surface attached communities of bacteria held together by self-produced polymer matrixs mainly composed of polysaccharides, secreted proteins, and extracellular DNAs. Bacterial biofilm formation is a complex process and can be described in five main phases: (i) reversible attachment phase, where bacteria non-specifically attach to surfaces; (ii) irreversible attachment phase, which involves interaction between bacterial cells and a surface using bacterial adhesins such as fimbriae and lipopolysaccharide (LPS); (iii) production of extracellular polymeric substances (EPS) by the resident bacterial cells; (iv) biofilm maturation phase, in which bacterial cells synthesize and release signaling molecules to sense the presence of each other, conducing to the formation of microcolony and maturation of biofilms; and (v) dispersal/detachment phase, where the bacterial cells depart biofilms and comeback to independent planktonic lifestyle. Biofilm formation is detrimental in healthcare, drinking water distribution systems, food, and marine industries, etc. As a result, current studies have been focused toward control and prevention of biofilms. In an effort to get rid of harmful biofilms, various techniques and approaches have been employed that interfere with bacterial attachment, bacterial communication systems (quorum sensing, QS), and biofilm matrixs. Biofilms, however, also offer beneficial roles in a variety of fields including applications in plant protection, bioremediation, wastewater treatment, and corrosion inhibition amongst others. Development of beneficial biofilms can be promoted through manipulation of adhesion surfaces, QS and environmental conditions. This review describes the events involved in bacterial biofilm formation, lists the negative and positive aspects associated with bacterial biofilms, elaborates the main strategies currently used to regulate establishment of harmful bacterial biofilms as well as certain strategies employed to encourage formation of beneficial bacterial biofilms, and highlights the future perspectives of bacterial biofilms.

/pdf/beyond-risk-bacterial-biofilms-and-their-regulating-4xnboj91j5.pdf

Beyond Risk: Bacterial Biofilms and Their Regulating Approaches.

Pseudomonas aeruginosa is a major health challenge that causes recalcitrant multidrug-resistant infections, especially in immunocompromised and hospitalized patients P aeruginosa is an important cause of nosocomial and ventilator-associated pneumonia characterized by high prevalence and fatality rates P aeruginosa also causes chronic lung infections in individuals with cystic fibrosis Multidrug- and totally drug-resistant strains of P aeruginosa are increasing threats that contribute to high mortality in these patients The pathogenesis of many P aeruginosa infections depends on its ability to form biofilms, structured bacterial communities that can coat mucosal surfaces or invasive devices These biofilms make conditions more favorable for bacterial persistence, as embedded bacteria are inherently more difficult to eradicate than planktonic bacteria The molecular mechanisms that underlie P aeruginosa biofilm pathogenesis and the host response to P aeruginosa biofilms remain to be fully defined However, it is known that biofilms offer protection from the host immune response and are also extremely recalcitrant to antimicrobial therapy Therefore, development of novel therapeutic strategies specifically aimed at biofilms is urgently needed Here, we review the host response, key clinical implications of P aeruginosa biofilms, and novel therapeutic approaches to treat biofilms relevant to lung infections Greater understanding of P aeruginosa biofilms will elucidate novel avenues to improve outcomes for P aeruginosa pulmonary infections

/pdf/pseudomonas-aeruginosa-biofilms-host-response-and-clinical-uwdw9ng3dh.pdf

Pseudomonas aeruginosa Biofilms: Host Response and Clinical Implications in Lung Infections.

Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.

/pdf/interference-in-bacterial-quorum-sensing-a-biopharmaceutical-4e2yhd4tmo.pdf

Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective.

Biotechnological applications of quorum quenching enzymes.

Pseudomonas aeruginosa is a Gram negative pathogenic bacteria involved in many human infections including otitis, keratitis, pneumonia and diabetic foot ulcers. P. aeruginosa uses a communication system, referred to as quorum sensing (QS), to adopt a group behaviour by synchronizing the expression of certain genes. Among the regulated traits, secretion of proteases or siderophores, motility and biofilm formation are mainly involved in the pathogenicity. Many efforts have been dedicated to the development of quorum sensing inhibitors (QSI) and quorum quenching (QQ) agents to disrupt QS. QQ enzymes have been particularly considered as they may act in a catalytic way without entering the cell. Here we focus on the lactonase SsoPox which was previously investigated for its ability to degrade the signalling molecules, acyl-homoserine lactones, in particular on the engineered variant SsoPox-W263I. We highlight the potential of SsoPox-W263I to inhibit the virulence of 51 clinical P. aeruginosa isolates from diabetic foot ulcers by decreasing the secretion of two virulence factors, proteases and pyocyanin, as well as biofilm formation. We further compared the effect of SsoPox-W263I to the comprehensively described QSI, 5-fluorouracil and C-30. We found the lactonase SsoPox-W263I to be significantly more effective than the tested QSI at their respective concentration optimum and to retain its activity after immobilisation steps, paving the way for future therapeutic applications.

/pdf/effect-of-quorum-quenching-lactonase-in-clinical-isolates-of-2h0aan08nk.pdf

Effect of Quorum Quenching Lactonase in Clinical Isolates of Pseudomonas aeruginosa and Comparison with Quorum Sensing Inhibitors.

Extremozymes have gained considerable interest as they could meet industrial requirements. Among these, SsoPox is a hyperthermostable enzyme isolated from the archaeon Sulfolobus solfataricus. This enzyme is a lactonase catalyzing the hydrolysis of acyl-homoserine lactones; these molecules are involved in Gram-negative bacterial communication referred to as quorum sensing. SsoPox exhibits promiscuous phosphotriesterase activity for the degradation of organophosphorous chemicals including insecticides and chemical warfare agents. Owing to its bi-functional catalytic abilities as well as its intrinsic stability, SsoPox is appealing for many applications, having potential uses in the agriculture, defense, food and health industries. Here we investigate the biotechnological properties of the mutant SsoPox-W263I, a variant with increased lactonase and phosphotriesterase activities. We tested enzyme resistance against diverse process-like and operating conditions such as heat resistance, contact with organic solvents, sterilization, storage and immobilization. Bacterial secreted materials from both Gram-negative and positive bacteria were harmless on SsoPox-W263I activity and could reactivate heat-inactivated enzyme. SsoPox showed resistance to harsh conditions demonstrating that it is an extremely attractive enzyme for many applications. Finally, the potential of SsoPox-W263I to be active at subzero temperature is highlighted and discussed in regards to the common idea that hyperthermophile enzymes are nearly inactive at low temperatures.

/pdf/harnessing-hyperthermostable-lactonase-from-sulfolobus-2m0wj5uad3.pdf

Laure Plener

Papers

Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective.

Biotechnological applications of quorum quenching enzymes.

Effect of Quorum Quenching Lactonase in Clinical Isolates of Pseudomonas aeruginosa and Comparison with Quorum Sensing Inhibitors.

Harnessing hyperthermostable lactonase from Sulfolobus solfataricus for biotechnological applications

Engineering acyl-homoserine lactone-interfering enzymes toward bacterial control.