Outsmarting superbugs: bactericidal activity of nanostructured titanium surfaces against methicillin- and gentamicin-resistantStaphylococcus aureusATCC 33592

2019 ◽  
Vol 7 (28) ◽  
pp. 4424-4431 ◽  
Author(s):  
Jason V. Wandiyanto ◽  
Samuel Cheeseman ◽  
Vi Khanh Truong ◽  
Mohammad Al Kobaisi ◽  
Chantal Bizet ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bactericidal Activity ◽  
Pathogenic Bacteria ◽  
Rapid Rise ◽  
Significant Issue ◽  
Nanostructured Titanium ◽  
Biomaterial Surfaces ◽  
Titanium Surfaces

The colonisation of biomaterial surfaces by pathogenic bacteria is a significant issue of concern, particularly in light of the rapid rise of antibiotic resistance.

scholarly journals The Fate of Osteoblast-Like MG-63 Cells on Pre-Infected Bactericidal Nanostructured Titanium Surfaces

Materials ◽  
2019 ◽  
Vol 12 (10) ◽  
pp. 1575 ◽  
Author(s):  
Jason V. Wandiyanto ◽  
Vi Khanh Truong ◽  
Mohammad Al Kobaisi ◽  
Saulius Juodkazis ◽  
Helmut Thissen ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Titanium Implants ◽  
The Body ◽  
Eukaryotic Cells ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Load Bearing ◽  
Nanostructured Titanium ◽  
Nanostructured Surfaces ◽  
Titanium Surfaces

Biomaterials that have been newly implanted inside the body are the substratum targets for a “race for the surface”, in which bacterial cells compete against eukaryotic cells for the opportunity to colonize the surface. A victory by the former often results in biomaterial-associated infections, which can be a serious threat to patient health and can undermine the function and performance of the implant. Moreover, bacteria can often have a ‘head start’ if implant contamination has taken place either prior to or during the surgery. Current prevention and treatment strategies often rely on systemic antibiotic therapies, which are becoming increasingly ineffective due to a growing prevalence of antibiotic-resistant bacteria. Nanostructured surfaces that kill bacteria by physically rupturing bacterial cells upon contact have recently emerged as a promising solution for the mitigation of bacterial colonization of implants. Furthermore, these nanoscale features have been shown to enhance the adhesion and proliferation of eukaryotic cells, which is a key to, for example, the successful osseointegration of load-bearing titanium implants. The bactericidal activity and biocompatibility of such nanostructured surfaces are often, however, examined separately, and it is not clear to what extent bacterial cell-surface interactions would affect the subsequent outcomes of host-cell attachment and osseointegration processes. In this study, we investigated the ability of bactericidal nanostructured titanium surfaces to support the attachment and growth of osteoblast-like MG-63 human osteosarcoma cells, despite them having been pre-infected with pathogenic bacteria. MG-63 is a commonly used osteoblastic model to study bone cell viability, adhesion, and proliferation on the surfaces of load-bearing biomaterials, such as titanium. The nanostructured titanium surfaces used here were observed to kill the pathogenic bacteria, whilst simultaneously enhancing the growth of MG-63 cells in vitro when compared to that occurring on sterile, flat titanium surfaces. These results provide further evidence in support of nanostructured bactericidal surfaces being used as a strategy to help eukaryotic cells win the “race for the surface” against bacterial cells on implant materials.

scholarly journals Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii

2021 ◽  
Vol 22 (2) ◽  
pp. 571
Author(s):  
Viviana De Luca ◽  
Andrea Petreni ◽  
Alessio Nocentini ◽  
Andrea Scaloni ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Selective Inhibition ◽  
Extensive Study ◽  
Protein Isoforms ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Microbial Survival ◽  
Reversible Hydration

Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials.

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

scholarly journals Sorting out the Superbugs: Potential of Sortase A Inhibitors among Other Antimicrobial Strategies to Tackle the Problem of Antibiotic Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 164 ◽  
Author(s):  
Nikita Zrelovs ◽  
Viktorija Kurbatska ◽  
Zhanna Rudevica ◽  
Ainars Leonchiks ◽  
Davids Fridmanis
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Surface Proteins ◽  
Sortase A ◽  
Inhibitory Compounds ◽  
Alternative Means ◽  
Alternative Approaches ◽  
Conventional Antibiotics

Rapid spread of antibiotic resistance throughout the kingdom bacteria is inevitably bringing humanity towards the “post-antibiotic” era. The emergence of so-called “superbugs”—pathogen strains that develop resistance to multiple conventional antibiotics—is urging researchers around the globe to work on the development or perfecting of alternative means of tackling the pathogenic bacteria infections. Although various conceptually different approaches are being considered, each comes with its advantages and drawbacks. While drug-resistant pathogens are undoubtedly represented by both Gram(+) and Gram(−) bacteria, possible target spectrum across the proposed alternative approaches of tackling them is variable. Numerous anti-virulence strategies aimed at reducing the pathogenicity of target bacteria rather than eliminating them are being considered among such alternative approaches. Sortase A (SrtA) is a membrane-associated cysteine protease that catalyzes a cell wall sorting reaction by which surface proteins, including virulence factors, are anchored to the bacterial cell wall of Gram(+) bacteria. Although SrtA inhibition seems perspective among the Gram-positive pathogen-targeted antivirulence strategies, it still remains less popular than other alternatives. A decrease in virulence due to inactivation of SrtA activity has been extensively studied in Staphylococcus aureus, but it has also been demonstrated in other Gram(+) species. In this manuscript, results of past studies on the discovery of novel SrtA inhibitory compounds and evaluation of their potency were summarized and commented on. Here, we discussed the rationale behind the inhibition of SrtA, raised some concerns on the comparability of the results from different studies, and touched upon the possible resistance mechanisms as a response to implementation of such therapy in practice. The goal of this article is to encourage further studies of SrtA inhibitory compounds.

scholarly journals Antibacterial Compounds from Mushrooms: A Lead to Fight ESKAPEE Pathogenic Bacteria?

Planta Medica ◽  
2020 ◽  
Author(s):  
Violette Hamers ◽  
Clément Huguet ◽  
Mélanie Bourjot ◽  
Aurélie Urbain
Keyword(s):  
Antibiotic Resistance ◽  
Global Health ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Pathogenic Microorganisms ◽  
Bacterial Strains ◽  
Antibacterial Compounds ◽  
New Antibiotics ◽  
Hospital Stays ◽  
Antibacterial Potential

AbstractInfectious diseases are among the greatest threats to global health in the 21st century, and one critical concern is due to antibiotic resistance developed by an increasing number of bacterial strains. New resistance mechanisms are emerging with many infections becoming more and more difficult if not impossible to treat. This growing phenomenon not only is associated with increased mortality but also with longer hospital stays and higher medical costs. For these reasons, there is an urgent need to find new antibiotics targeting pathogenic microorganisms such as ESKAPEE bacteria. Most of currently approved antibiotics are derived from microorganisms, but higher fungi could constitute an alternative and remarkable reservoir of anti-infectious compounds. For instance, pleuromutilins constitute the first class of antibiotics derived from mushrooms. However, macromycetes still represent a largely unexplored source. Publications reporting the antibacterial potential of mushroom extracts are emerging, but few purified compounds have been evaluated for their bioactivity on pathogenic bacterial strains. Therefore, the aim of this review is to compile up-to-date data about natural products isolated from fruiting body fungi, which significantly inhibit the growth of ESKAPEE pathogenic bacteria. When available, data regarding modes of action and cytotoxicity, mandatory when considering a possible drug development, have been discussed in order to highlight the most promising compounds.

scholarly journals Long-lasting renewable antibacterial porous polymeric coatings enable titanium biomaterials to prevent and treat peri-implant infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuyi Wu ◽  
Jianmeng Xu ◽  
Leiyan Zou ◽  
Shulu Luo ◽  
Run Yao ◽  
...  
Keyword(s):  
Dental Implant ◽  
Pathogenic Bacteria ◽  
Titanium Surface ◽  
Polymeric Coating ◽  
Antibacterial Efficacy ◽  
Polymeric Coatings ◽  
Implant Infection ◽  
Titanium Surfaces

AbstractPeri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.

scholarly journals Bacteria and Their Antibiotic Resistance Profiles in Ambient Air in Accra, Ghana, February 2020: A Cross-Sectional Study

2021 ◽  
Vol 6 (3) ◽  
pp. 110
Author(s):  
Godfred Saviour Kudjo Azaglo ◽  
Mohammed Khogali ◽  
Katrina Hann ◽  
John Alexis Pwamang ◽  
Emmanuel Appoh ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Ambient Air ◽  
Cross Sectional Study ◽  
Bacillus Species ◽  
Resistant Bacteria ◽  
Cross Sectional ◽  
Antibiotic Resistant ◽  
Bacterial Counts ◽  
Inappropriate Use

Inappropriate use of antibiotics has led to the presence of antibiotic-resistant bacteria in ambient air. There is no published information about the presence and resistance profiles of bacteria in ambient air in Ghana. We evaluated the presence and antibiotic resistance profiles of selected bacterial, environmental and meteorological characteristics and airborne bacterial counts in 12 active air quality monitoring sites (seven roadside, two industrial and three residential) in Accra in February 2020. Roadside sites had the highest median temperature, relative humidity, wind speed and PM10 concentrations, and median airborne bacterial counts in roadside sites (115,000 CFU/m3) were higher compared with industrial (35,150 CFU/m3) and residential sites (1210 CFU/m3). Bacillus species were isolated in all samples and none were antibiotic resistant. There were, however, Pseudomonas aeruginosa, Escherichia coli, Pseudomonas species, non-hemolytic Streptococci, Coliforms and Staphylococci species, of which six (50%) showed mono-resistance or multidrug resistance to four antibiotics (penicillin, ampicillin, ciprofloxacin and ceftriaxone). There was a positive correlation between PM10 concentrations and airborne bacterial counts (rs = 0.72), but no correlations were found between PM10 concentrations and the pathogenic bacteria nor their antibiotic resistance. We call for the expansion of surveillance of ambient air to other cities of Ghana to obtain nationally representative information.

scholarly journals COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics

2021 ◽  
Vol 22 (13) ◽  
pp. 6891
Author(s):  
João S. Rebelo ◽  
Célia P. F. Domingues ◽  
Francisco Dionisio ◽  
Manuel C. Gomes ◽  
Ana Botelho ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Human Microbiome ◽  
Antibiotic Resistance Genes ◽  
Public Health Problem ◽  
Small World ◽  
Physical Contact ◽  
Hygiene Measures

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal–Wallis and Dunn’s pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

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