scholarly journals Ribosome Protection Proteins—“New” Players in the Global Arms Race with Antibiotic-Resistant Pathogens

2021 ◽  
Vol 22 (10) ◽  
pp. 5356
Author(s):  
Rya Ero ◽  
Xin-Fu Yan ◽  
Yong-Gui Gao
Keyword(s):  
Bacterial Infections ◽  
Significant Proportion ◽  
Resistance Mechanism ◽  
Inhibitory Effect ◽  
Resistance Mechanisms ◽  
Human Pathogens ◽  
Antibiotic Resistant ◽  
Long Time ◽  
Life Threatening ◽  
A Minor

Bacteria have evolved an array of mechanisms enabling them to resist the inhibitory effect of antibiotics, a significant proportion of which target the ribosome. Indeed, resistance mechanisms have been identified for nearly every antibiotic that is currently used in clinical practice. With the ever-increasing list of multi-drug-resistant pathogens and very few novel antibiotics in the pharmaceutical pipeline, treatable infections are likely to become life-threatening once again. Most of the prevalent resistance mechanisms are well understood and their clinical significance is recognized. In contrast, ribosome protection protein-mediated resistance has flown under the radar for a long time and has been considered a minor factor in the clinical setting. Not until the recent discovery of the ATP-binding cassette family F protein-mediated resistance in an extensive list of human pathogens has the significance of ribosome protection proteins been truly appreciated. Understanding the underlying resistance mechanism has the potential to guide the development of novel therapeutic approaches to evade or overcome the resistance. In this review, we discuss the latest developments regarding ribosome protection proteins focusing on the current antimicrobial arsenal and pharmaceutical pipeline as well as potential implications for the future of fighting bacterial infections in the time of “superbugs.”

scholarly journals Co-selection of antibiotic and heavy metal resistance in freshwater bacteria

2016 ◽  
Vol 75 (s2) ◽  
Author(s):  
Andrea Di Cesare ◽  
Ester Eckert ◽  
Gianluca Corno
Keyword(s):  
Heavy Metal ◽  
Resistance Genes ◽  
Heavy Metal Resistance ◽  
Resistance Mechanisms ◽  
Metal Resistance ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Selection Of

<p class="p1">Antibiotic resistant bacteria are found in most environments, especially in highly anthropized waters. A direct correlation between human activities (<em><span class="s1">e.g., </span></em>pollution) and spread and persistence of antibiotic resistant bacteria (ARB) and resistance genes (ARGs) within the resident bacterial communities appears more and more obvious. Furthermore, the threat posed for human health by the presence of ARB and ARGs in these environments is enhanced by the risk of horizontal gene transfer of resistance genes to human pathogens. Although the knowledge on the spread of antibiotic resistances in waters is increasing, the understanding of the driving factors determining the selection for antibiotic resistance in the environment is still scarce. Antibiotic pollution is generally coupled with contamination by heavy metals (HMs) and other chemicals, which can also promote the development of resistance mechanisms, often through co-selecting for multiple resistances. The co-selection of heavy metal resistance genes and ARGs in waters, sediments, and soils, increases the complexity of the ecological role of ARGs, and reduces the effectiveness of control actions. In this mini-review we present the state-of-the-art of the research on antibiotic- and HM-resistance and their connection in the environment, with a focus on HM pollution and aquatic environments. We review the spread and the persistence of HMs and/or ARB, and how it influences their respective gene co-selection. In the last chapter, we propose Lake Orta, a system characterized by an intensive HM pollution followed by a successful restoration of the chemistry of the water column, as a study-site to evaluate the spread and selection of HMs and antibiotic resistances in heavily disturbed environments.</p>

scholarly journals Antibiotic Resistance. Scale and Relevance of Studies of the Antibiotic-Resistant Isolates Circulation among Children

2021 ◽  
Vol 6 (4) ◽  
pp. 199-207
Author(s):  
I. I. Fohel ◽  
◽  
M. V. Kryvtsova ◽  
Y. Y. Bugir
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Pediatric Population ◽  
Public Awareness ◽  
World Health ◽  
Antibiotic Resistant ◽  
Rapid Acquisition ◽  
The World ◽  
Life Threatening

Over the last decade, the phenomenon of antibiotic resistance of microorganisms has become a global problem for modern medicine around the world. Bacteria quickly acquire genes of resistance to the action of the antibiotics. Bacterial infections that used to be easy to treat, now, in some cases, can even be life-threatening. Resistant microorganisms pose a danger not only among the adult population but also among the pediatric population. According to the World Health Organization, up to 200,000 newborns die each year from infections caused by antibiotic-resistant microorganisms. Premature babies are at particular risk because their immune systems are still underdeveloped. The use of antibiotics in children should be reasonably approached, as recent studies have shown an increase of the spread of bacteria with resistance genes. Infections caused by resistant microorganisms are more difficult to treat and require special methods and approaches, especially for children, where the choice of antibiotics is already limited. The purpose of the study is to analyze the literature for the current state of the problem of antibiotic resistance, prospects for future development, relevance in pediatric practice. Materials and methods. The research materials are publications of national and foreign authors. Analytical methods were used as main research methods. This article considers the problem of antibiotic resistance, general mechanisms of its formation, research data on the prevalence of circulation of resistant strains in the pediatric population and their role in the initiation of resistant bacterial infections. Conclusion. It is concluded that bacteria insensitive to antibiotics are quite common among the pediatric population and in some cases are life-threatening. This phenomenon requires constant monitoring in order to detect and correctly treat persistent bacterial infections. There are many strains resistant to first- and second-generation antibiotics circulating in children. In some cases, the treatment of certain conditions in pediatrics may lead to the use of reserve antibiotics. Systemic coordinated work around the world and an individual approach in determining the sensitivity of microorganisms to antibiotics in each case can prevent the rapid acquisition of resistance genes by bacteria. It is also necessary to spread information about the threat of antibiotic resistance in order to raise public awareness and counteract the empirical use of antibiotics at home without a prescription. There is also an urgent need to invent new chemical compounds with bactericidal properties as soon as possible

scholarly journals γδ T Lymphocytes in Asthma: a Complicated Picture

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Michał K. Zarobkiewicz ◽  
Ewelina Wawryk-Gawda ◽  
Wioleta Kowalska ◽  
Mariola Janiszewska ◽  
Agnieszka Bojarska-Junak
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Human Subjects ◽  
Γδ T Cells ◽  
Mice Model ◽  
Health Related ◽  
Life Threatening ◽  
A Minor

AbstractA minor subset (approximately 5%) of peripheral T cells has their TCR build up from γ and δ chains instead of α and β—those are the γδ T lymphocytes. They can be functionally divided into subsets, e.g., Th1-, Th2-, Th9-, Th17-, Tfh-, and Treg-like γδ T cells. They share some specifics of both innate and adaptive immunity, and are capable of rapid response to a range of stimuli, including some viral and bacterial infections. Atopic diseases, including asthma, are one of major health-related problems of modern western societies. Asthma is one of the most common airway diseases, affecting people of all ages and having potential life-threatening consequences. In this paper, we review the current knowledge about the involvement of γδ T cells in the pathogenesis of asthma and its exacerbations. We summarize both the studies performed on human subjects as well as on the murine model of asthma. γδ T cells seem to be involved in the pathogenesis of asthma, different subsets probably perform opposite functions, e.g., symptom-exacerbating Vγ1 and symptom-suppressing Vγ4 in mice model of asthma.

scholarly journals Mechanism of BceAB-type transporter: Resistance by lipid II flipping

2020 ◽  
Author(s):  
Julia Zaschke-Kriesche ◽  
Sandra Unsleber ◽  
Irina Voitsekhovskaia ◽  
Andreas Kulik ◽  
Lara V. Behrmann ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Streptococcus Agalactiae ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Human Pathogenic Bacteria ◽  
Lipid Ii ◽  
Multiresistant Bacteria

AbstractTreatment of bacterial infections are the great challenge of our era due to the evolved resistance mechanisms against antibiotics. The Achilles heel of bacteria is the cell wall especially during the needs of its synthesis and cell division. Here lipid II is an essential cell wall precursor component synthesized in the cytosol and flipped into the outer leaflet of the membrane prior to its incorporation into the cell wall.Compounds targeting the cell wall or its biosynthesis precursors have been around for decades and have been used as antibiotics against bacterial infections like meningitis, pneumonia and endocarditis. Antimicrobial peptides (AMPs) have proven to be a promising weapon against multiresistant bacteria. However, the Bacitracin efflux (BceAB)-type ATP binding cassette transporters expressed in the membrane of human pathogenic bacteria have been shown to confer resistance to these alternative antibiotics, thereby hampering their medical development.In Streptococcus agalactiae COH1 the BceAB-type transporter NsrFP (SaNsrFP) confers high-level resistance against the antimicrobial peptide nisin, a member of the lantibiotic subfamily. We showed that SaNsrFP provides a novel resistance mechanism by flipping lipid II back into the cytosol, thereby preventing the binding of nisin as well as other lipid II targeting compounds. This is intriguing since a relatively simple reaction mediates resistance to human pathogenic bacteria to lipid II targeting antibiotics, regardless of their structure.Significance StatementThe ABC-transporter NsrFP from Streptococcus agalactiae (SaNsrFP) belongs to the BceAB-type transporters. Several BceAB-type transporters are known to confer resistance against multiple antimicrobial peptides. In this study a new resistance mechanism was identified, which is based on the reduction of the number of cell wall precursor lipid II molecules on the cell surface mediated by SaNsrFP. SaNsrFP flips lipid II, which are considered to be the target for many antibiotics, back into the cytoplasm. With this newly gained knowledge about the resistance mechanism of BceAB-type transporters, novel strategies can be established to overcome or bypass this resistance in human pathogenic bacteria.

scholarly journals Antiquorum from Freshwater Zoosporic Isolated Fungi: Maximization of some Ameliorative Factors

2014 ◽  
Vol 63 (4) ◽  
pp. 433-441
Author(s):  
ESSAM MOHAMED AHMED ◽  
MOHAMED IBRAHIM FARAG AMMAR
Keyword(s):  
Bacterial Infections ◽  
Inhibitory Effect ◽  
Quadratic Model ◽  
Human Pathogens ◽  
Experimental Medium ◽  
Cultural Conditions ◽  
Factorial Model ◽  
Statistical Strategy ◽  
Zoosporic Fungi ◽  
Screening Study

Many bacteria detect their critical cell numbers through a mechanism known as quorum sensing (QS). Acyl homoserine lactones (AHLs) mediated QS systems have been shown to operate in important human pathogens. The aim of this study was to evaluate the inhibitory effect generated by zoosporic freshwater fungi on AHLs production. A potent strain of zoosporic fungi, Leptolegniella keratinophilum, was isolated after extended screening study. A new cheap medium was used to support the anti-AHLs activities. Statistical strategy depending on two levels factorial model and three levels quadratic model were applied to guide a production maximization process. The three levels Box-Behnken model possessed the ability to optimize the significant nutritional and cultural conditions and to predict the maximum that can be achieved. In the course of study, we reached 88% anti-AHLs activity, while the initial activity was 63%. There was no previous maximization methodology for either the experimental medium, or the fungi. The results suggest that freshwater zoosporic fungi can be potentially used against bacterial infections.

scholarly journals Polymeric Composites with Silver (I) Cyanoximates Inhibit Biofilm Formation of Gram-Positive and Gram-Negative Bacteria

Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1018 ◽  
Author(s):  
S. R. Lotlikar ◽  
E. Gallaway ◽  
T. Grant ◽  
S. Popis ◽  
M. Whited ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Dry Weight ◽  
Polymeric Composites ◽  
Bactericidal Effect ◽  
Inhibitory Effect ◽  
Human Pathogens ◽  
Gram Positive ◽  
Biofilm Growth ◽  
Gram Negative ◽  
Biofilm Development

Biofilms are surface-associated microbial communities known for their increased resistance to antimicrobials and host factors. This resistance introduces a critical clinical challenge, particularly in cases associated with implants increasing the predisposition for bacterial infections. Preventing such infections requires the development of novel antimicrobials or compounds that enhance bactericidal effect of currently available antibiotics. We have synthesized and characterized twelve novel silver(I) cyanoximates designated as Ag(ACO), Ag(BCO), Ag(CCO), Ag(ECO), Ag(PiCO), Ag(PICO) (yellow and red polymorphs), Ag(BIHCO), Ag(BIMCO), Ag(BOCO), Ag(BTCO), Ag(MCO) and Ag(PiPCO). The compounds exhibit a remarkable resistance to high intensity visible light, UV radiation and heat and have poor solubility in water. All these compounds can be well incorporated into the light-curable acrylate polymeric composites that are currently used as dental fillers or adhesives of indwelling medical devices. A range of dry weight % from 0.5 to 5.0 of the compounds was tested in this study. To study the potential of these compounds in preventing planktonic and biofilm growth of bacteria, we selected two human pathogens (Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus) and Gram-positive environmental isolate Bacillus aryabhattai. Both planktonic and biofilm growth was abolished completely in the presence of 0.5% to 5% of the compounds. The most efficient inhibition was shown by Ag(PiCO), Ag(BIHCO) and Ag(BTCO). The inhibition of biofilm growth by Ag(PiCO)-yellow was confirmed by scanning electron microscopy (SEM). Application of Ag(BTCO) and Ag(PiCO)-red in combination with tobramycin, the antibiotic commonly used to treat P. aeruginosa infections, showed a significant synergistic effect. Finally, the inhibitory effect lasted for at least 120 h in P. aeruginosa and 36 h in S. aureus and B. aryabhattai. Overall, several silver(I) cyanoximates complexes efficiently prevent biofilm development of both Gram-negative and Gram-positive bacteria and present a particularly significant potential for applications against P. aeruginosa infections.

scholarly journals Characterization of the nucleotide-binding domain NsrF from the BceAB-type ABC-transporter NsrFP from the human pathogen Streptococcus agalactiae

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fabia Furtmann ◽  
Nicola Porta ◽  
Dai Tri Hoang ◽  
Jens Reiners ◽  
Julia Schumacher ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Bacterial Infections ◽  
Nucleotide Binding ◽  
Resistance Mechanisms ◽  
Binding Domain ◽  
Binding Modes ◽  
Human Pathogens ◽  
Nucleotide Binding Domain ◽  
Transporter Family

Abstract Treatment of bacterial infections is a great challenge of our era due to the various resistance mechanisms against antibiotics. Antimicrobial peptides are considered to be potential novel compound as antibiotic treatment. However, some bacteria, especially many human pathogens, are inherently resistant to these compounds, due to the expression of BceAB-type ABC transporters. This rather new transporter family is not very well studied. Here, we report the first full characterization of the nucleotide binding domain of a BceAB type transporter from Streptococcus agalactiae, namely SaNsrF of the transporter SaNsrFP, which confers resistance against nisin and gallidermin. We determined the NTP hydrolysis kinetics and used molecular modeling and simulations in combination with small angle X-ray scattering to obtain structural models of the SaNsrF monomer and dimer. The fact that the SaNsrFH202A variant displayed no ATPase activity was rationalized in terms of changes of the structural dynamics of the dimeric interface. Kinetic data show a clear preference for ATP as a substrate, and the prediction of binding modes allowed us to explain this selectivity over other NTPs.

scholarly journals Tailored Liposomal Nanotraps for the Treatment of Streptococcal Infections

2020 ◽  
Author(s):  
Hervé Besançon ◽  
Viktoriia Babiychuk ◽  
Yu Larpin ◽  
René Köffel ◽  
Dominik Schittny ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Diagnostic Delay ◽  
Host Cells ◽  
Streptococcal Toxic Shock Syndrome ◽  
Streptococcal Infections ◽  
Antibiotic Resistant ◽  
Bacterial Diseases ◽  
Life Threatening ◽  
Streptococcus Dysgalactiae Subspecies Equisimilis ◽  
Pathogen Clearance

Abstract Background: Streptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize - by competitive sequestration - numerous exotoxins. Results: In this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis - pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens. Conclusions: Unravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.

scholarly journals Inhibitory Effect of Bacteriophages Isolated from Sewage Water in the City of Kirkuk on some Types of Human Pathogenic Bacteria

2017 ◽  
Vol 14 (4) ◽  
pp. 727-734 ◽  
Author(s):  
Baghdad Science Journal
Keyword(s):  
Pathogenic Bacteria ◽  
Inhibitory Effect ◽  
Sewage Water ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Salmonella Spp ◽  
Antibiotic Resistant ◽  
E Coli ◽  
New Antibiotics ◽  
The City

Most approaches to combat antibiotic resistant bacteria concentrate on discovering new antibiotics or modifying existing ones. However, one of the most promising alternatives is the use of bacteriophages. This study was focused on the isolation of bacteriophages that are specific to some of commonly human pathogens namely E. coli, Streptococcus pyogenes, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Klebsiella pneumoniae. These bacteriophages were isolated from sewages that were collected from four different locations in Kirkuk City. Apart from S. pyogenes, bacteriophages specific to all tested bacteria were successfully isolated and tested for their effectiveness by spot test. The most effective bacteriophages that were isolated from sewages and sewage water of Al-Jumhori Hospital compared to other sites. It is concluded that the sewage water of hospitals represents a perfect environment for these bacteriophages.

scholarly journals Pimpinella Anisum Extracts, Safe Anti-Bacterial Treatment

2021 ◽  
Author(s):  
Mahdieh Soltani ◽  
Asal khodagholi ◽  
Zahra Farjami ◽  
Mohammad Mehdi Akbarin
Keyword(s):  
Herbal Product ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Alcohol Extract ◽  
Pimpinella Anisum ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Long Time ◽  
Bacterial Treatment

Abstract Introduction: Now a day, antibiotic-resistant bacteria are increasing and became a medical worldwide problem, therefore the achievement of a new safe disinfectant is deemed necessary. Pimpinella anisum (Pa) is an aromatic plant, belonging to the Umbelliferae family. It is a well-known traditional medicinal herb that has been used in old medicine as an antibacterial, anticancer, antiulcer, therefore, the aim of this study is evaluation of the anti-bacterial effect of PA extracts against Probiotics and pathogens bacteria. Method: 96-well microplates MICs were determined by the broth microdilution method. Five Serial dilutions from 50 to 1 μg/mL concentrations were admitted for all bacteria which include: Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923, and Probiotics complex. Results: PA watery extract demonstrates a statically inhibitory effect in just 50 g/L concentration against E.Coli, E. Faecalis, and Probiotic p= 0.000 for all, whereas this concentration was 25 g/L for Staph. Aureus and Pu p=0.000 and p= 0.007 respectively. PA alcohol extract displays the same effect in 1g/L for all bacteria p= 0.000 for all bacteria. Conclusion: Our results showed that PA in both watery and Alcohol extractions can inhibit both pathogenic and non-pathogen bacteria whereas active compounds are alcohol soluble. Long-time consumption of PA in an herbal product could disrupt normal bacteria of the gastrointestinal system while PA watery extract can promote Probiotics.

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