scholarly journals Escaping from ESKAPE. Clinical Significance and Antibiotic Resistance Mechanisms in Acinetobacter baumannii: a Review

2020 ◽  
Vol 11 (1) ◽  
pp. 8190-8203
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Antimicrobial Agents ◽  
Genetic Resistance ◽  
Resistance Mechanisms ◽  
Genomic Islands ◽  
Resistant Bacteria ◽  
Clinical Settings

Antibiotic resistance represents a critical threat in clinical settings nowadays, with an essential ecological dimension. Due to the involvement of the resistance genes, this phenomenon has gained an unprecedented expansion. Their accumulation and dissemination are facilitated by mobile genetic elements (MGEs) (plasmids, transposons, integrons, genomic islands) that can increase intracellular DNA mobility. In clinical settings, one of the critical resistant bacteria associated with nosocomial infections is Acinetobacter baumannii. This Gram-negative bacterium exhibits variate resistance mechanisms that enable it to survive in extreme environmental conditions and to evade antimicrobial agents. The enormous adaptive capacity and the essential role in the emergence of severe nosocomial infections lead to the need to study more deeply the mechanisms involved in antibiotic resistance in A. baumannii strains. In this review, we will initially present the role of A. baumannii in human and veterinary infectious pathology. We will subsequently discuss the main genetic resistance mechanisms (both intrinsic and acquired) encountered in A. baumannii strains.

scholarly journals Quinolone Resistance Reversion by Targeting the SOS Response

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
E. Recacha ◽  
J. Machuca ◽  
P. Díaz de Alba ◽  
M. Ramos-Güelfo ◽  
F. Docobo-Pérez ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Agents ◽  
Sos Response ◽  
Resistance Mechanisms ◽  
Quinolone Resistance ◽  
Resistant Bacteria ◽  
Health Crisis ◽  
E Coli ◽  
Isogenic Strains

ABSTRACT Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated E. coli mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated E. coli mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response.

scholarly journals The Use of Liquids Ionic Fluids as Pharmaceutically Active Substances Helpful in Combating Nosocomial Infections Induced by Klebsiella Pneumoniae New Delhi Strain, Acinetobacter Baumannii and Enterococcus Species

2018 ◽  
Vol 19 (9) ◽  
pp. 2779 ◽  
Author(s):  
Andrzej Miskiewicz ◽  
Piotr Ceranowicz ◽  
Mateusz Szymczak ◽  
Krzysztof Bartuś ◽  
Paweł Kowalczyk
Keyword(s):  
European Union ◽  
Antibiotic Resistance ◽  
Ionic Liquids ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Resistant Bacteria ◽  
New Delhi ◽  
The European Union ◽  
Enterococcus Species

This review deals with various microbiological activities of ionic liquids, which constitute the first anti-infective defense against multi-drug-resistant bacteria—with a particular emphasis placed on medicine and pharmacology. The quoted data on the biological activity of ionic liquids including their antimicrobial properties (depending on the type of a cation or an anion) and are discussed in view of possible applications in nosocomial infections. Dedicated attention is given to finding infections with the Klebsiella pneumoniae New Delhi strain, Acinetobacter baumannii, and Enterococcus species, which are responsible for the induction of antibiotic resistance in intensive care units. Diagnosis and treatment using current antibiotics is a significant problem in hospital care, and the relevant burden on the health systems of the European Union member states induces the search for new, effective methods of treatment. Ionic liquids, due to their antibacterial effect, can be considered topical and general medications and may provide the basis for treatment to eliminate the antibiotic resistance phenomenon in the future. At present, the number of infections with resistant pathogens in hospitals and outpatient clinics in the European Union is growing. In 2015–2017, a significant incidence of respiratory and bloodstream infections with bacteria resistant to antibiotics from the 3rd generation group of cephalosporins, glycopeptides, and carbapenems were observed. The paper presents examples of synthesized bifunctional salts with at least one pharmaceutically active ion in obtaining a controlled release, controlled delivery, and biological impact on the pathogenic bacteria, viruses and fungi. The ionic liquids obtained in the presented way may find applications in the treatment of wounds and infections.

The relationship between the phageome and human health: are bacteriophages beneficial or harmful microbes?

2021 ◽  
pp. 1-14
Author(s):  
L. Fernández ◽  
A.C. Duarte ◽  
A. Rodríguez ◽  
P. García
Keyword(s):  
Antibiotic Resistance ◽  
Human Health ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Negative Impact ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Potential Risks

In the context of the global antibiotic resistance crisis, bacteriophages are increasingly becoming promising antimicrobial agents against multi-resistant bacteria. Indeed, a huge effort is being made to bring phage-derived products to the market, a process that will also require revising the current regulations in order to facilitate their approval. However, despite the evidence supporting the safety of phages for humans, the general public would still be reluctant to use ‘viruses’ for therapeutic purposes. In this scenario, we consider that it is important to discuss the role of these microorganisms in the equilibrium of the microbiota and how this relates to human health. To do that, this review starts by examining the role of phages as key players in bacterial communities (including those that naturally inhabit the human body), modulating the species composition and contributing to maintain a ‘healthy’ status quo. Additionally, in specific situations, e.g. an infectious disease, bacteriophages can be used as target-specific antimicrobials against pathogenic bacteria (phage therapy), while being harmless to the desirable microbiota. Apart from that, incipient research shows the potential application of these viruses to treat diseases caused by bacterial dysbiosis. This latter application would be comparable to the use of probiotics or prebiotics, since bacteriophages can indirectly improve the growth of beneficial bacteria in the gastrointestinal tract by removing undesirable competitors. On the other hand, possible adverse effects do not appear to be an impediment to promote phage therapy. Nonetheless, it is important to remember their potentially negative impact, mainly concerning their immunogenicity or their potential spread of virulence and antibiotic resistance genes, especially by temperate phages. Overall, we believe that phages should be largely considered beneficial microbes, although it is paramount not to overlook their potential risks.

Development of Peptides that Inhibit Aminoglycoside-Modifying Enzymes and β-Lactamases for Control of Resistant Bacteria

2020 ◽  
Vol 21 (10) ◽  
pp. 1011-1026
Author(s):  
Bruna O. Costa ◽  
Marlon H. Cardoso ◽  
Octávio L. Franco
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Specific Chemical ◽  
Target Interaction ◽  
Multiresistant Bacteria ◽  
Acute Bacterial Infections

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.

scholarly journals Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 671
Author(s):  
Federica Giacometti ◽  
Hesamaddin Shirzad-Aski ◽  
Susana Ferreira
Keyword(s):  
Antibiotic Resistance ◽  
Food Safety ◽  
Antimicrobial Resistance ◽  
Food Processing ◽  
Resistance Mechanisms ◽  
Human Environment ◽  
Real Risk ◽  
Cross Adaptation ◽  
Novel Approaches

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

2020 ◽  
Vol 41 (04) ◽  
pp. 455-469 ◽  
Author(s):  
Charles Feldman ◽  
Ronald Anderson
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Bacterial Pathogen ◽  
Epidemiological Data ◽  
The United States ◽  
Invasive Infection ◽  
Geographic Variations ◽  
The Impact

AbstractWith the notable exceptions of the United States and Canada in particular, the global burden of disease in adults due to invasive infection with the dangerous respiratory, bacterial pathogen, Streptococcus pneumoniae (pneumococcus) remains. This situation prevails despite the major successes of inclusion of polysaccharide conjugate vaccines (PCVs) in many national childhood immunization programs and associated herd protection in adults, as well as the availability of effective antimicrobial agents. Accurate assessment of the geographic variations in the prevalence of invasive pneumococcal disease (IPD) has, however, been somewhat impeded by the limitations imposed on the acquisition of reliable epidemiological data due to reliance on often insensitive, laboratory-based, pathogen identification procedures. This, in turn, may result in underestimation of the true burden of IPD and represents a primary focus of this review. Other priority topics include the role of PCVs in the changing epidemiology of IPD in adults worldwide, smoking as a risk factor not only in respect of increasing susceptibility for development of IPD, but also in promoting pneumococcal antibiotic resistance. The theme of pneumococcal antibiotic resistance has been expanded to include mechanisms of resistance to commonly used classes of antibiotics, specifically β-lactams, macrolides and fluoroquinolones, and, perhaps somewhat contentiously, the impact of resistance on treatment outcome. Finally, but no less importantly, the role of persistent antigenemia as a driver of a chronic, subclinical, systemic proinflammatory/procoagulant phenotype that may underpin the long-term sequelae and premature mortality of those adults who have recovered from an episode of IPD, is considered.

The Activity of Alkanna Species in vitro Culture and Intact Plant Extracts Against Antibiotic Resistant Bacteria

2019 ◽  
Vol 25 (16) ◽  
pp. 1861-1865 ◽  
Author(s):  
Naira Sahakyan ◽  
Margarit Petrosyan ◽  
Armen Trchounian
Keyword(s):  
Antibiotic Resistance ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Plant Origin ◽  
Bacterial Strains ◽  
Biotechnological Production ◽  
Antibiotic Resistant

Overcoming the antibiotic resistance is nowadays a challenge. There is still no clear strategy to combat this problem. Therefore, the urgent need to find new sources of antibacterial agents exists. According to some literature, substances of plant origin are able to overcome bacterial resistance against antibiotics. Alkanna species plants are among the valuable producers of these metabolites. But there is a problem of obtaining the standardized product. So, this review is focused on the discussion of the possibilities of biotechnological production of antimicrobial agents from Alkanna genus species against some microorganisms including antibiotic resistant bacterial strains.

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