scholarly journals A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

2021 ◽  
Vol 11 ◽  
Author(s):  
Fazal Mehmood Khan ◽  
Vijay Singh Gondil ◽  
Changchang Li ◽  
Mengwei Jiang ◽  
Junhua Li ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Therapeutic Agents ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
High Antibacterial Activity ◽  
A Genome ◽  
Rapid Spread ◽  
Conventional Antibiotics ◽  
Myoviridae Family

The rapid spread and emergence of multidrug-resistant Acinetobacter baumannii and other pathogenic Gram-negative bacteria spurred scientists and clinicians to look for alternative therapeutic agents to conventional antibiotics. In the present study, an A. baumannii bacteriophage p54 was isolated and characterized. Morphological and genome analysis revealed that bacteriophage p54 belongs to Myoviridae family with a genome size of 165,813 bps. A novel endolysin, namely LysAB54, showing low similarity with other well-known related endolysins, was cloned, expressed, and characterized from the bacteriophage p54. LysAB54 showed significant bactericidal activity against multidrug-resistant A. baumannii and other Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, in the absence of outer membrane permeabilizers. Based on all those observations, LysAB54 could represent a potential agent for the treatment of multidrug-resistant Gram-negative superbugs.

An Overview of the Activities of Cefiderocol Against Sensitive and Multidrug- Resistant (MDR) Bacteria

2020 ◽  
Vol 20 (18) ◽  
pp. 1908-1916
Author(s):  
Manaf AlMatar ◽  
Osman Albarri ◽  
Essam A. Makky ◽  
Işıl Var ◽  
Fatih Köksal
Keyword(s):  
Multidrug Resistant ◽  
Therapeutic Agents ◽  
Health Concern ◽  
Side Chain ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Public Health Concern ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
The Public

The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other β-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of β-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. İn this article, an overview of the recent studies on cefiderocol was presented.

scholarly journals Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of Lipopolysaccharide Production

2010 ◽  
Vol 54 (12) ◽  
pp. 4971-4977 ◽  
Author(s):  
Jennifer H. Moffatt ◽  
Marina Harper ◽  
Paul Harrison ◽  
John D. F. Hale ◽  
Evgeny Vinogradov ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Lipid A ◽  
Multidrug Resistant ◽  
Complete Loss ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Lipid A Biosynthesis ◽  
Initial Binding ◽  
Derivatives Of ◽  
Global Health Problem

ABSTRACT Infections caused by multidrug-resistant (MDR) Gram-negative bacteria represent a major global health problem. Polymyxin antibiotics such as colistin have resurfaced as effective last-resort antimicrobials for use against MDR Gram-negative pathogens, including Acinetobacter baumannii. Here we show that A. baumannii can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid A component of lipopolysaccharide (LPS), which has long been considered to be essential for the viability of Gram-negative bacteria. We characterized 13 independent colistin-resistant derivatives of A. baumannii type strain ATCC 19606 and showed that all contained mutations within one of the first three genes of the lipid A biosynthesis pathway: lpxA, lpxC, and lpxD. All of these mutations resulted in the complete loss of LPS production. Furthermore, we showed that loss of LPS occurs in a colistin-resistant clinical isolate of A. baumannii. This is the first report of a spontaneously occurring, lipopolysaccharide-deficient, Gram-negative bacterium.

scholarly journals Effects of Lipidation on a Proline-Rich Antibacterial Peptide

2021 ◽  
Vol 22 (15) ◽  
pp. 7959
Author(s):  
Federica Armas ◽  
Adriana Di Stasi ◽  
Mario Mardirossian ◽  
Antonello A. Romani ◽  
Monica Benincasa ◽  
...  
Keyword(s):  
De Novo ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
C Terminus ◽  
Proline Rich Peptide ◽  
Conventional Antibiotics

The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in E. coli after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents.

scholarly journals Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter baumannii Way

2021 ◽  
Vol 9 (7) ◽  
pp. 1353
Author(s):  
Arianna Pompilio ◽  
Daniela Scribano ◽  
Meysam Sarshar ◽  
Giovanni Di Bonaventura ◽  
Anna Teresa Palamara ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Public Health Problem ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Abiotic Surfaces ◽  
Healthcare Associated

Bacterial biofilms are a serious public-health problem worldwide. In recent years, the rates of antibiotic-resistant Gram-negative bacteria associated with biofilm-forming activity have increased worrisomely, particularly among healthcare-associated pathogens. Acinetobacter baumannii is a critically opportunistic pathogen, due to the high rates of antibiotic resistant strains causing healthcare-acquired infections (HAIs). The clinical isolates of A. baumannii can form biofilms on both biotic and abiotic surfaces; hospital settings and medical devices are the ideal environments for A. baumannii biofilms, thereby representing the main source of patient infections. However, the paucity of therapeutic options poses major concerns for human health infections caused by A. baumannii strains. The increasing number of multidrug-resistant A. baumannii biofilm-forming isolates in association with the limited number of biofilm-eradicating treatments intensify the need for effective antibiofilm approaches. This review discusses the mechanisms used by this opportunistic pathogen to form biofilms, describes their clinical impact, and summarizes the current and emerging treatment options available, both to prevent their formation and to disrupt preformed A. baumannii biofilms.

scholarly journals Ceftazidime-avibactam: new rules for the game against multidrug-resistant gram-negative bacteria

2018 ◽  
Vol 20 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Roman S. Kozlov ◽  
Olga U. Stetsiouk ◽  
Irina V. Andreeva
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Efficacy And Safety ◽  
Gram Negative ◽  
Rapid Spread ◽  
The World ◽  
Insight Into ◽  
Lactamase Inhibitor ◽  
Real Clinical Practice

The rapid spread of multidrug-resistant Gram-negative bacteria in hospital settings all over the world makes a demand for the new options to overcome antimicrobial resistance. Ceftazidime-avibactam is the first approved antibiotic that contains a new beta-lactamase inhibitor with unique properties. This review provides insight into the spectrum of activity, pharmacological characteristics, data on efficacy and safety of ceftazidime-avibactam obtained from the clinical trials and real clinical practice, as well as prospects for further studies and clinical application of this new antimicrobial agent.

scholarly journals Comparison of clinical characteristics and outcomes of bloodstream infections due to multidrug-resistant Acinetobacter baumannii and other Gram-negative bacteria in ICU patients

2020 ◽  
Author(s):  
Ying Qian ◽  
Yongpeng Xie ◽  
Haifeng Mao ◽  
Jiguang Li ◽  
Caihong Gu ◽  
...  
Keyword(s):  
Septic Shock ◽  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Clinical Characteristics ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Apache Ii Score ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli

Abstract Background: Multidrug-resistant (MDR) bloodstream infection (BSI) by Gram-negative bacteria (GNB) is an important cause of mortality in the intensive care unit (ICU). The purpose of this study was to compare the clinical characteristics of some GNB BSIs and to analyze their drug resistance, with an emphasis on the analysis of prognostic risk factors related to MDR-Acinetobacter baumannii (A. baumannii) BSI.Methods: A retrospective study was conducted in the ICU of lianyungang hospital in China. Patients with BSIs due to MDR-A. baumannii, MDR-Klebsiella pneumoniae (K. pneumoniae), MDR-Pseudomonas aeruginosa (P. aeruginosa) and MDR-Escherichia coli (E. coli) were included.Results: The overall drug resistance rate to imipenem of A. baumannii and K. pneumoniae was significantly higher than that of P. aeruginosa and E. coli (95.8% and 75.5% vs 44.6% and 9.2% respectively). The mortality rates were 71.9%, 63.3%, 41.5% and 38.1%, respectively. The multivariate analysis of MDR-A. baumannii BSI, APACHE II score, hormone use, development of septic shock were associated with the 30-day mortality, while high albumin level with survival.Conclusion: The treatment of MDR-A. baumannii and MDR-K. pneumoniae infection resulted difficult due to their high drug resistance rate. However, the understanding of the clinical characteristics of different BSIs might be helpful to predict, to some extent, the pathogenic bacteria involved so as to proceed with an early sensitive antibiotic treatment. The high mortality rate due to BSI MDR-A. baumannii might be correlated with APACHE II score, nutritional status, and hormone therapy, while septic shock was a warning sign of poor prognosis.

scholarly journals Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Anna Vickers ◽  
Shazad Mushtaq ◽  
Neil Woodford ◽  
Michel Doumith ◽  
David M. Livermore
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protein Synthesis ◽  
Acinetobacter Baumannii ◽  
Ribosomal Subunit ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Protein Synthesis Inhibitors ◽  
Gram Negative ◽  
Content Type ◽  
Active Analog

ABSTRACT Pyrrolocytosines RX-04A to -D are designed to bind to the bacterial 50S ribosomal subunit differently from currently used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A—the most active analog—inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa at 0.5 to 4 μg/ml, with no MICs of >8 μg/ml. MICs for multidrug-resistant (MDR) carbapenemase producers were up to 2-fold higher than those for control strains; values were highest for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs.

scholarly journals Rapid Spread and Control of Multidrug-Resistant Gram-Negative Bacteria in COVID-19 Patient Care Units

2021 ◽  
Vol 27 (4) ◽  
Author(s):  
Ashka Patel ◽  
Michele Emerick ◽  
Marie K. Cabunoc ◽  
Michelle H. Williams ◽  
Michael Anne Preas ◽  
...  
Keyword(s):  
Patient Care ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Rapid Spread ◽  
And Control

scholarly journals Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 284 ◽  
Author(s):  
Nataliia Antonova ◽  
Daria Vasina ◽  
Anastasiya Lendel ◽  
Evgeny Usachev ◽  
Valentine Makarov ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Salmonella Typhi ◽  
Therapeutic Agents ◽  
Gram Negative Bacteria ◽  
Bacterial Isolates ◽  
Gram Negative ◽  
Rapid Spread ◽  
Osmotic Lysis ◽  
Eskape Pathogens

The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called “post-antibiotic era” in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria. In this study, we present the results of in vitro activity assays of three putative and newly cloned Myoviridae bacteriophage endolysins (LysAm24, LysECD7, and LysSi3). The chosen proteins represent lysins with diverse domain organization (single-domain vs. two-domain) and different predicted mechanisms of action (lysozyme vs. peptidase). The enzymes were purified, and their properties were characterized. The enzymes were tested against a panel of Gram-negative clinical bacterial isolates comprising all Gram-negative representatives of the ESKAPE group. Despite exhibiting different structural organizations, all of the assayed lysins were shown to be capable of lysing Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi strains. Less than 50 μg/mL was enough to eradicate growing cells over more than five orders of magnitude. Thus, LysAm24, LysECD7, and LysSi3 represent promising therapeutic agents for drug development.

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