Search Results (9)

Advances in affordable genetic engineering have accelerated the creation and large-scale environmental release of genetically modified microorganisms (GMMs). While beneficial applications exist, GMMs may present unique, long-term risks to human and environmental health. Unlike static chemicals, GMMs are biologically active, self-replicating entities capable of rapid mutation and global dispersal. Current regulatory frameworks place responsibility on each country to regulate GMMs, without a clear, coordinated international policy. This review details critical risk scenarios, including horizontal gene transfer to native species and the possible disruption of vital human microbiomes (gut, oral, and infant), which could increase resistance to degradation, promote traits that expand a microbe’s range of hosts or ecological niches, and enhance the production of novel metabolites with unexpected biological activity. In soil, GMMs may support the emergence of “super bugs” or destabilize carbon sequestration cycles, potentially impacting climate resilience. Engineered microbial enzymes in the food supply may also act as environmental drivers of autoimmunity. Given the limited understanding of microbial ecology, we propose a decision-based biosafety workflow emphasizing pre-release risk assessment and continuous post-release monitoring. We urge national and international regulators to adopt the precautionary principle to better protect human health and the environment from the potential negative outcomes of GMMs. Full article

The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a key factor to consider in the optimization of this therapy. In this sense, four corroles were designed to study how the number of cationic centers can influence the efficacy of antibacterial photodynamic treatments. First, 5,10,15-Tris(pentafluorophenyl)corrole (Co) and 5,15-bis(pentafluorophenyl)-10-(4-(trifluoromethyl)phenyl)corrole (Co-CF₃) were synthesized, and then derivatized by nucleophilic aromatic substitution with 2-dimethylaminoethanol and 2-(dimethylamino)ethylamine, obtaining corroles Co-3NMe₂ and Co-CF₃-2NMe₂, respectively. The straightforward synthetic strategy gave rise to macrocycles with different numbers of tertiary amines that can acquire positive charges in an aqueous medium by protonation at physiological pH. Spectroscopic and photodynamic studies demonstrated that their properties as chromophores and photosensitizers were unaffected, regardless of the substituent groups on the periphery. All tetrapyrrolic macrocycles were able to produce reactive oxygen species (ROS) by both photodynamic mechanisms. Uptake experiments, the level of ROS produced in vitro, and PDI treatments mediated by these compounds were assessed against clinical strains: methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. In vitro experiments indicated that the peripheral substitution significantly affected the uptake of the photosensitizers by microbes and, consequently, the photoinactivation performance. Co-3NMe₂ was the most effective in killing both Gram-positive and Gram-negative bacteria (inactivation > 99.99%). This work lays the foundations for the development of new corrole derivatives having pH-activable cationic groups and with plausible applications as effective broad-spectrum antimicrobial photosensitizers. Full article

Global rise of infections and deaths caused by drug-resistant bacterial pathogens are among the unmet medical needs. In an age of drying pipeline of novel antibiotics to treat bacterial infections, antimicrobial peptides (AMPs) are proven to be valid therapeutics modalities. Direct in vivo applications of many AMPs could be challenging; however, works are demonstrating encouraging results for some of them. In this review article, we discussed 3-D structures of potent AMPs e.g., polymyxin, thanatin, MSI, protegrin, OMPTA in complex with bacterial targets and their mode of actions. Studies on human peptide LL37 and de novo-designed peptides are also discussed. We have focused on AMPs which are effective against drug-resistant Gram-negative bacteria. Since treatment options for the infections caused by super bugs of Gram-negative bacteria are now extremely limited. We also summarize some of the pertinent challenges in the field of clinical trials of AMPs. Full article

Multidrug-resistant Acinetobacter baumannii, particularly those producing carbapenemases, are spread worldwide. A reliable detection of carbapenemases is essential to choose the appropriate antimicrobial therapy and, consequently, prevent the dissemination of carbapenem-resistant strains. The aim of this study is to examine the molecular basis of the carbapenem resistance mechanism and estimation of conventional PCR and real-time PCR usefulness for the detection of oxacillinases when compared to phenotypic carbapenemases detection. The following methods were evaluated: the CarbAcineto NP test, Carbapenem Inactivation Method, CPO panels of semiautomated antimicrobial susceptibility testing method on the BD Phoenix™ M50 system, conventional Polymerase Chain Reaction and real-time PCR. The eazyplex^® SuperBug complete A assay was used as the reference method. Among the tested strains, 39 (67.2%) carried the bla_OXA-40 gene, while the bla_OXA-23 gene was noted amongst 19 (32.8%) isolates. The diagnostic sensitivities of the studied assays were as follows: CarbAcineto NP—65.5%; CIM—100%; CPO—100%; conventional PCR—100%; real-time PCR—100%. Full article

Increasing antimicrobial resistance of Gram-negative rods is an important diagnostic, clinical and epidemiological problem of modern medicine. Therefore, it is important to detect multi-drug resistant strains as early on as possible. This study aimed to evaluate Eazyplex^® SuperBug CRE assay usefulness for beta-lactamase gene detection among Gram-negative rods, directly from urine samples and positive blood cultures. The Eazyplex^® SuperBug CRE assay is based on a loop-mediated isothermal amplification of genetic material and allows for the detection of a selection of genes encoding carbapenemases, KPC, NDM, VIM, OXA-48, OXA-181 and extended-spectrum beta-lactamases from the CTX-M-1 and CTX-M-9 groups. A total of 120 clinical specimens were included in the study. The test gave valid results for 58 (96.7%) urine samples and 57 (95.0%) positive blood cultures. ESBL and/or carbapenemase enzymes genes were detected in 56 (93.3%) urine and 55 (91.7%) blood samples, respectively. The Eazyplex^® SuperBug CRE assay can be used for a rapid detection of the genes encoding the most important resistance mechanisms to beta-lactams in Gram-negative rods also without the necessity of bacterial culture. Full article

Natural products play vital roles against infectious diseases since ancient times and most drugs in use today are derived from natural sources. Worldwide, multi-drug resistance becomes a massive threat to the society with increasing mortality. Hence, it is very crucial to identify alternate strategies to control these ‘super bugs’. Pseudomonas aeruginosa is an opportunistic pathogen reported to be resistant to a large number of critically important antibiotics. Quorum sensing (QS) is a cell–cell communication mechanism, regulates the biofilm formation and virulence factors that endow pathogenesis in various bacteria including P. aeruginosa. In this study, we identified and evaluated quorum sensing inhibitors (QSIs) from plant-based natural products against P. aeruginosa. In silico studies revealed that catechin-7-xyloside (C7X), sappanol and butein were capable of interacting with LasR, a LuxR-type quorum sensing regulator of P. aeruginosa. In vitro assays suggested that these QSIs significantly reduced the biofilm formation, pyocyanin, elastase, and rhamnolipid without influencing the growth. Especially, butein reduced the biofilm formation up to 72.45% at 100 µM concentration while C7X and sappanol inhibited the biofilm up to 66% and 54.26% respectively. Microscale thermophoresis analysis revealed that C7X had potential interaction with LasR (K_D = 933±369 nM) and thermal shift assay further confirmed the biomolecular interactions. These results suggested that QSIs are able to substantially obstruct the P. aeruginosa QS. Since LuxR-type transcriptional regulator homologues are present in numerous bacterial species, these QSIs may be developed as broad spectrum anti-infectives in the future. Full article

The emergence and spread of Carbapenem-resistant Enterobacteriaceae (CRE) is seriously posing threats in effective healthcare delivery. The aim of this study was to ascertain the emergence of CRE at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH) Awka. Biological samples were collected from 153 consenting patient from 5 clinics in the hospital. The isolates were identified using standard microbiological protocols. Susceptibility to meropenem was done using Kirby-Bauer disc diffusion method on Mueller Hinton Agar. A total of 153 patients were recruited in this study. About one half of those from rural, 63.64% from Sub-urban and 42.27% from urban areas had significant E. coli and Klebsiella spp infections. The male: female ratio of the Enterobacteriaceae infection was 1:1. Almost as much inpatient as outpatient study participants had the infections. The infections were observed mostly on participants with lower educational status. The unmarried individuals were most infected compared to their married counterparts. Enterobacteriaceae infection rate was 50.98%. Of this, 28.21% had CRE infection while the overall prevalence of the CRE in the studied population was 14.38% (22/153). This study shows that CRE is quickly emerging in both community and hospital environments. Klebsiella spp was the most common CRE in this hospital especially Klebsiella oxytoca. Hospitalization was a strong risk factor in the CRE infections. Rapid and accurate detection is critical for their effective management and control. Full article

Antibiotic overuse is one of the major drivers in the generation of antibiotic resistant “super bugs” that can potentially cause serious effects on health. In this study, we reported that the polycationic polysaccharide, chitosan could improve the efficacy of a given antibiotic (gentamicin) to combat bacterial biofilms, the universal lifestyle of microbes in the world. Short- or long-term treatment with the mixture of chitosan and gentamicin resulted in the dispersal of Listeria monocytogenes (L. monocytogenes) biofilms. In this combination, chitosan with a moderate molecular mass (~13 kDa) and high N-deacetylation degree (~88% DD) elicited an optimal anti-biofilm and bactericidal activity. Mechanistic insights indicated that chitosan facilitated the entry of gentamicin into the architecture of L. monocytogenes biofilms. Finally, we showed that this combination was also effective in the eradication of biofilms built by two other Listeria species, Listeria welshimeri and Listeria innocua. Thus, our findings pointed out that chitosan supplementation might overcome the resistance of Listeria biofilms to gentamicin, which might be helpful in prevention of gentamicin overuse in case of combating Listeria biofilms when this specific antibiotic was recommended. Full article