An official website of the United States government
Abstract Drug‐resistant microorganisms cause serious problems in human healthcare, leading to the persistence in infections and poor treatment outcomes from conventional therapy. In this study, a gene‐targeting strategy using microbubble‐controlled nanoparticles is introduced that can effectively eliminate biofilms of methicillin‐resistantStaphylococcus aureus(MRSA) in vivo. Biofilm‐targeting nanoparticles (BTN) capable of delivering oligonucleotides are developed that effectively remove biofilm‐associated bacteria upon controlled delivery with diatom‐based microbubblers (MB). The activity of BTN in silencing key bacterial genes related to MRSA biofilm formation (icaA), bacterial growth (ftsZ), and antimicrobial resistance (mecA), as well as their multi‐targeting ability in vitro is validated. The integration of BTN with MB is next examined, resulting in synergistic effects in biofilm removal and antimicrobial activity in an ex vivo porcine skin model. The therapeutic efficacy is further investigated in vivo in a mouse wound model infected with MRSA biofilm, which showed that MB‐controlled BTN delivery substantially reduced bacterial load and led to the effective elimination of the biofilm. This study underscores the potential of the gene silencing platform with physical enhancement as a promising strategy to combat problems related to biofilms and antibiotic resistance.
more »
« less
An Overview of Biofilm Formation–Combating Strategies and Mechanisms of Action of Antibiofilm Agents
Biofilm formation on surfaces via microbial colonization causes infections and has become a major health issue globally. The biofilm lifestyle provides resistance to environmental stresses and antimicrobial therapies. Biofilms can cause several chronic conditions, and effective treatment has become a challenge due to increased antimicrobial resistance. Antibiotics available for treating biofilm-associated infections are generally not very effective and require high doses that may cause toxicity in the host. Therefore, it is essential to study and develop efficient anti-biofilm strategies that can significantly reduce the rate of biofilm-associated healthcare problems. In this context, some effective combating strategies with potential anti-biofilm agents, including plant extracts, peptides, enzymes, lantibiotics, chelating agents, biosurfactants, polysaccharides, organic, inorganic, and metal nanoparticles, etc., have been reviewed to overcome biofilm-associated healthcare problems. From their extensive literature survey, it can be concluded that these molecules with considerable structural alterations might be applied to the treatment of biofilm-associated infections, by evaluating their significant delivery to the target site of the host. To design effective anti-biofilm molecules, it must be assured that the minimum inhibitory concentrations of these anti-biofilm compounds can eradicate biofilm-associated infections without causing toxic effects at a significant rate.
more »
« less
- PAR ID:
- 10390932
- Date Published:
- Journal Name:
- Life
- Volume:
- 12
- Issue:
- 8
- ISSN:
- 2075-1729
- Page Range / eLocation ID:
- 1110
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Group BStreptococcus(GBS) is an encapsulated Gram‐positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short‐chain sugars that have recently been shown to possess antimicrobial and anti‐biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO‐dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular‐type‐ and sequence‐type‐specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST‐1, ST‐12, ST‐19, and ST‐23 strains. Interestingly, CpsIa as well as ST‐7 and ST‐17 were not susceptible to the anti‐biofilm activity of HMOs, underscoring the strain‐specific effects of these important antimicrobial molecules against the perinatal pathogenStreptococcus agalactiae.more » « less
-
Surgical site infections (SSIs) are a leading cause of morbidity and mortality and a significant expense to the healthcare system and hospitals. The majority of these infections are preventable; however, increasing bacterial resistance, biofilm persistence, and human error contribute to the occurrence of these healthcare-associated infections. We present a flexible antimicrobial blue-light emitting bandage designed for use on postoperative incisions and wounds. The photonic device is designed to inactivate bacteria present on the skin and prevent bacterial colonization of the site, thus reducing the occurrence of SSIs. This antimicrobial light emitting bandage uses blue light’s proven abilities to inactivate a wide range of clinical pathogens regardless of their resistance to antibiotics, inactivate bacteria without harming mammalian cells, improve wound healing, and inactivate bacteria in biofilms. The antimicrobial bandage consists of a thin 2”x2” silicone sheet with an array of 77 LEDs embedded in multiple layers of the material for thermal management. The 405 nm center wavelength LED array is designed to be a wearable device that integrates with standard hospital infection prevention protocols. The device was characterized for irradiance of 44.5 mW/cm2. Methicillin-resistant Staphylococcus aureus seeded in a petri dish was used to evaluate bacterial inactivation in vitro. Starting with a concentration of 2.16 x 107 colony forming units (CFU)/mL, 45% of the bacteria was inactivated within 15 minutes, 65% had been inactivated by 30 minutes, 99% was inactivated by 60 minutes, and a 7 log reduction and complete sterilization was achieved within 120 minutes.more » « less
-
Abstract Streptococcus agalactiaeor Group BStreptococcus(GBS) is a Gram‐positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants. However, human milk has also been shown to have protective effects against infection; a characteristic that is likely derived from antimicrobial and immunomodulatory properties of molecules that comprise human milk. Recent evidence suggests that human milk oligosaccharides (HMOs), short‐chain sugars that comprise 8–20 % of breast milk, have antimicrobial and anti‐biofilm activity against GBS and other bacterial pathogens. Additionally, HMOs have been shown to potentiate the activity of antibiotics against GBS. This review presents the most recent published work that studies the interaction between HMOs and GBS.more » « less
-
Biofilms are the cause of most chronic bacterial infections. Living within the biofilm matrix, which is made of extracellular substances, including polysaccharides, proteins, eDNA, lipids and other molecules, provides microorganisms protection from antimicrobials and the host immune response. Exopolysaccharides are major structural components of bacterial biofilms and are thought to be vital to numerous aspects of biofilm formation and persistence, including adherence to surfaces, coherence with other biofilm-associated cells, mechanical stability, protection against desiccation, binding of enzymes, and nutrient acquisition and storage, as well as protection against antimicrobials, host immune cells and molecules, and environmental stressors. However, the contribution of specific exopolysaccharide types to the pathogenesis of biofilm infection is not well understood. In this study we examined whether the absence of the two main exopolysaccharides produced by the biofilm former Pseudomonas aeruginosa would affect wound infection in a mouse model. Using P. aeruginosa mutants that do not produce the exopolysaccharides Pel and/or Psl we observed that the severity of wound infections was not grossly affected; both the bacterial load in the wounds and the wound closure rates were unchanged. However, the size and spatial distribution of biofilm aggregates in the wound tissue were significantly different when Pel and Psl were not produced, and the ability of the mutants to survive antibiotic treatment was also impaired. Taken together, our data suggest that while the production of Pel and Psl do not appear to affect P. aeruginosa pathogenesis in mouse wound infections, they may have an important implication for bacterial persistence in vivo.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/life12081110
