•The spread of resistant bacteria and the development bacterial biofilm have been two major challenges.•Biofilm infections are notoriously difficult to treat, as the matrix provides physical ...protection.•Phototherapy including photothermal therapy and photodynamic therapy has attracted wide attentions.•This review describes the latest phototherapy strategies to resist resistant bacteria and biofilms infections.
The spread of resistant bacteria and the development bacterial biofilm have been two major challenges in the application of biomaterials, causing device failure as well as tissue infections. The overuse of antibiotics has become a common cause of the emergence of multiple antibiotics-resistant bacteria. Besides, biofilm infections are notoriously difficult to treat, as the biofilm matrix provides physical protection from antibiotic treatment. Recently, nanomaterials with high drug loading capacity, various types of stimuli responsiveness, smart targeting and small-size are able to increase local drug concentration and to escape the capture of macrophages. Especially, the loading of drugs to the nanomaterials enhances chances for macrophage capture which is a serious problem related to interaction with immune system. Phototherapy including photothermal therapy and photodynamic therapy has attracted wide attentions in treating infectious diseases as the development of drug-resistant bacteria and bacterial biofilms. In addition, based on the special microenvironment of bacterial infections, various construction and modification methods of nanomaterials showed high efficient antibacterial properties. This review describes the latest advances in the phototherapy strategies to resist resistant bacteria and biofilms related infections.
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•MAPC as a novel biofilm microenvironment-responsive nanoplatform can decompose in the acidic biofilm microenvironment and subsequently releases the α-amylase, manganese oxide and ...sonosensitizer.•MAPC released α-amylase can selectively degrade the extracellular polymeric substances of MRSA biofilms and further promotes the sonosensitizer penetration.•MAPC released manganese oxide with catalase-like activity can convert the overproduced H2O2 into O2 to relieve the hypoxic biofilm microenvironment, which significantly enhances the sonodynamic antimicrobial efficiency.•MAPC offers an effective therapeutic strategy for superior MRSA biofilm eradication efficiency of combining biofilm structure degradation with improved ultrasound-driven antimicrobial sonodynamic therapy by hypoxia relief.
Treatment of bacterial biofilms remains a great challenge in the clinic. Recently, ultrasound (US)-driven antimicrobial sonodynamic therapy (aSDT) has been considered as an emerging therapeutic strategy for the treatment of biofilm infections. However, the hypoxic microenvironment and restricted diffusion of sonosensitizers within biofilms substantially reduce the therapeutic efficacy of aSDT. Herein, a biofilm microenvironment-responsive nanoplatform was proposed to promote biofilm degradation and sonosensitizer penetration, and relieve the hypoxic microenvironment, thereby augmenting aSDT efficiency against bacterial biofilm infections. This nanoplatform was prepared by modifying manganese dioxide nanosheets (MNS) with α-amylase, polyethylene glycol (PEG), and chlorin e6 (Ce6) to form MNS-α-amylase/PEG-Ce6 nanosheets (MAPC). After delivery into biofilm-infected tissues, MAPC decompose in the acidic biofilm microenvironment to locally release α-amylase and Ce6. The α-amylase degrades the extracellular polymeric substances of biofilms to promote Ce6 penetration. In addition, the MNS catalyze the conversion of endogenously overproduced H2O2 into O2 in infected tissue and relieve the hypoxic microenvironment to further enhance antibiofilm efficacy of aSDT. Such biofilm degradation and hypoxia-relief enhanced aSDT show approximately 6.9 log units (99.99998%) reduction of bacteria within biofilms in vitro, and efficiently treat methicillin-resistant Staphylococcus aureus (MRSA) biofilms-infected mice. Overall, biofilm degradation improves sonosensitizer penetration and relieves the hypoxic biofilm microenvironment to enhance the effects of aSDT by MAPC. Thus, the use of this nanoplatform provides a promising strategy for combating bacterial biofilm-associated infections.
The great clinical significance of biofilm-associated infections and their inherent recalcitrance to antibiotic treatment urgently demand the development of novel antibiofilm strategies. In this ...regard, antimicrobial peptides (AMPs) are increasingly recognized as a promising template for the development of antibiofilm drugs. Indeed, owing to their main mechanism of action, which relies on the permeabilization of bacterial membranes, AMPs exhibit a strong antimicrobial activity also against multidrug-resistant bacteria and slow-growing or dormant biofilm-forming cells and are less prone to induce resistance compared to current antibiotics. Furthermore, the antimicrobial potency of AMPs can be highly increased by combining them with conventional (antibiotics) as well as unconventional bioactive molecules. Combination treatments appear particularly attractive in the case of biofilms since the heterogeneous nature of these microbial communities requires to target cells in different metabolic states (e.g., actively growing cells, dormant cells) and environmental conditions (e.g., acidic pH, lack of oxygen or nutrients). Therefore, the combination of different bioactive molecules acting against distinct biofilm components has the potential to facilitate biofilm control and/or eradication. The aim of this review is to highlight the most promising combination strategies developed so far to enhance the therapeutic potential of AMPs against bacterial biofilms. The rationale behind and beneficial outcomes of using AMPs in combination with conventional antibiotics, compounds capable of disaggregating the extracellular matrix, inhibitors of signaling pathways involved in biofilm formation (i.e., quorum sensing), and other peptide-based molecules will be presented and discussed.
Bacterial biofilms colonize chronic wounds and surfaces of medical devices, thus making the development of reliable methods for imaging and detection of biofilms crucial. Although fluorescent ...identification of bacteria is sensitive and non-destructive, the lack of biofilm-specific fluorescent dyes limits the application of this technique to biofilm detection. Here, we demonstrate, for the first time, that fluorescent glutathione-stabilized gold nanoclusters (GSH-AuNCs) without targeting ligands can specifically interact with extracellular matrix components of Gram-negative and Gram-positive bacterial biofilms resulting in fluorescent staining of bacterial biofilms. By contrast, fluorescent bovine serum albumin-stabilized gold nanoclusters and 11-mercaptoundecanoic acid – stabilized gold nanoclusters do not stain the extracellular matrix of biofilms. According to molecular docking studies, GSH-AuNCs show affinity to several targets in extracellular matrix, including amyloid-anchoring proteins, matrix proteins and polysaccharides. Some experimental evidence was obtained for the interaction of GSH-AuNCs with the lipopolysaccharide (LPS) that was isolated from the matrix of Azospirillum baldaniorum biofilms. Based on GSH-AuNCs properties, we propose a new fluorescent method for the measurement of biofilm biomass with a limit of detection 1.7 × 105 CFU/mL. The sensitivity of the method is 10-fold higher than the standard biofilm quantification with the crystal violet assay. There is a good linear relationship between the fluorescence intensity from the biofilms and the number of CFU from the biofilms in the range from 2.6 × 105 to 6.7 × 107 CFU/mL. The developed nanocluster-mediated method of biofilm staining was successfully applied for quantitative detection of biofilm formation on urinary catheter surface. The presented data suggest that fluorescent GSH-AuNCs can be used to diagnose medical device-associated infections.
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•Fluorescent glutathione-stabilized gold nanoclusters can interact with the extracellular matrix of bacterial biofilms.•According to molecular docking, gold nanoclusters show affinity to several targets in matrix.•The experimental evidence for the interaction of the nanolusters with matrix polysaccharide was obtained.•Gold nanoclusters are used for the imaging and detection of biofilms.
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Bacterial biofilm represents a protected mode of bacterial growth that significantly enhances the resistance to antibiotics. Poly lactic-co-glycolic acid (PLGA)-based nanoparticle ...delivery systems have been intensively investigated to combat the bacterial biofilms-associated infections. However, some drawbacks associated with current PLGA-based nanoformulations (e.g. the relatively low drug loading capability, premature burst release and/or incapability of on-demand release of cargos at the site of action) restrict the transition from the lab research to the clinical applications. One potent strategy to overcome the above-mentioned limitations is exploiting the unique properties of carbon quantum dots (CQDs) and combining CQDs with the conventional PLGA nanoparticles. In the present study, the CQDs were innovatively incorporated into PLGA nanoparticles by using a microfluidic method. The resulting CQD-PLGA hybrid nanoparticles presented good loading capability of azithromycin (a macrolide antibiotic, AZI) and tobramycin (an aminoglycoside antibiotic, TOB), and stimuli-responsive release of the cargos upon laser irradiation. Consequently, AZI-loaded CQD-PLGA hybrid nanoparticles showed chemo-photothermally synergistic anti-biofilm effects against P. aeruginosa biofilms. Additionally, the CQD-PLGA hybrid nanoparticles demonstrated good biocompatibility with the eukaryotic cells. Overall, the proof-of-concept of CQD-PLGA hybrid nanoparticles may open a new possibility in chemo-photothermal therapy against bacterial biofilms.
•Au-TNT generates O2 while releasing ROS under the action of ultrasound.•SDT-mediated Au-TNT has a killing effect on oral multi-species biofilm.•The SDT in a rat peri-implantitis model improves ...bacterial-induced inflammation.•Au-TNT has excellent physicochemical stability for further clinical application.
Peri-implant infection caused by bacterial biofilm is the main reason for dental implant repair failure. The success of controlling infection depends mainly on eliminating bacterial biofilm. However, traditional medicine therapy is not practical due to the growth of bacterial resistance. Recently, antibacterial sonodynamic therapy (aSDT) activated by ultrasound has been recognized as an emerging strategy for treating biofilm infections. In this study, an activatable nanoplatform (Au-TNT) fabricated on the implant surface is proposed for aSDT. Au-TNT could rapidly produce O2 under ultrasonic irradiation, which could relieve the hypoxic microenvironment of biofilm and improve the anti-biofilm efficiency of aSDT. Furthermore, it could generate singlet oxygen (1O2) and hydroxyl radicals (OH), resulting in a powerfully high antibacterial capacity for both single and multi-species pathogenic biofilms as assessed by bacterial survival rate, cell membrane rupture, biofilm metabolism and thickness. Meanwhile, Au-TNT exhibited excellent antibacterial ability in vivo with a 3 logs CFU decreased compared to the control group. Interestingly, it also showed that Au-TNT downregulated inflammatory factor levels and promoted bone repair. Thus, this study provides a sonodynamic-catalytic nanoplatform for efficient biofilm eradication and peri-implant infection treatment.
Bacterial conjugation, also referred to as bacterial sex, is a major horizontal gene transfer mechanism through which DNA is transferred from a donor to a recipient bacterium by direct contact. ...Conjugation is universally conserved among bacteria and occurs in a wide range of environments (soil, plant surfaces, water, sewage, biofilms, and host-associated bacterial communities). Within these habitats, conjugation drives the rapid evolution and adaptation of bacterial strains by mediating the propagation of various metabolic properties, including symbiotic lifestyle, virulence, biofilm formation, resistance to heavy metals, and, most importantly, resistance to antibiotics. These properties make conjugation a fundamentally important process, and it is thus the focus of extensive study. Here, we review the key steps of plasmid transfer by conjugation in Gram-negative bacteria, by following the life cycle of the F factor during its transfer from the donor to the recipient cell. We also discuss our current knowledge of the extent and impact of conjugation within an environmentally and clinically relevant bacterial habitat, bacterial biofilms.
Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds ...the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD(+)/NADH and NADP(+)/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only ∼7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA, the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.
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