scholarly journals Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter Baumannii

2021 ◽  
Author(s):  
Xi Chen ◽  
Miao Liu ◽  
Pengfei Zhang ◽  
Miao Xu ◽  
Weihao Yuan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Galleria Mellonella ◽  
Volume Ratio ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Bacterial Cells ◽  
Strain Specificity ◽  
Drug Resistant Bacteria

Bacteriophage-encoded depolymerases are responsible for degrading capsular polysaccharides (CPS), lipopolysaccharides (LPS) and exopolysachcharides (EPS) of the host bacteria during phage invasion. They have been considered as promising antivirulence agents in controlling bacterial infections, including those caused by drug-resistant bacteria. This feature inspires a hope of utilizing these enzymes to disarm the polysaccharide capsid of the bacterial cells, which then strengthens the action of antibiotics. Here we have identified, cloned, and expressed a depolymerase Dpo71 from a bacteriophage specific for the gram-negative (G-ve) bacterium Acinetobacter baumannii in the heterologous host E. coli. Dpo71 sensitizes the multidrug-resistant (MDR) A. baumannii to the host immune attack, and also acts as an adjuvant to assist or boost the action of antibiotics, for example colistin. Specifically, Dpo71 at 10 µg/ml enables a complete bacterial eradication by human serum at 50% volume ratio. Dpo71 inhibits biofilm formation and disrupts the pre-formed biofilm. Combination of Dpo71 could significantly enhance the antibiofilm activity of colistin, and improve the survival rate of A. baumannii infected Galleria mellonella. Dpo71 retains the strain-specificity of the parent phage from which Dpo71 is derived: the phage-sensitive A. baumannii strains respond to Dpo71 treatment, whereas the phage-insensitive strains do not. This indicates that Dpo71 indeed is responsible for the host specificity of bacteriophages. In summary, our work demonstrates the feasibility of using recombinant depolymerases as an antibiotic adjuvants to supplement the development of new antibacterials and to battle against MDR pathogens.

scholarly journals Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Private Investment ◽  
Therapeutic Index ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Delivery Systems ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

Tea: An anti-bacterial agent against drug resistant bacteria

2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Bacterial Agent ◽  
Drug Resistant Bacteria ◽  
Scientific World

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.

scholarly journals MULTIDRUG-RESISTANT AND EXTREMELY DRUG-RESISTANT BACTERIA: ARE WE FACING THE END OF THE ANTIBIOTIC ERA?

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
G.M. Rossolini
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Infectious Complications ◽  
Future Perspective ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Public Health Agencies ◽  
Drug Resistant Bacteria

Antibiotics are one of the most significant advancements of modern medicine. They have changed the prognosis of several bacterial infections, and made possible advanced medical practices associated with a high risk of infectious complications. Unfortunately, antibiotics are affected by the phenomenon of antibiotic resistance, which jeopardizes their efficacy. In recent years, antibiotic discovery and development has been lagging, due to a lower appeal of this sector for the pharmaceutical industry, while antibiotic resistance has continued to evolve with the eventual emergence and dissemination of bacterial strains which are resistant to most available antibiotics and pose a major challenge to antimicrobial chemotherapy. This worrisome scenario, indicated as the “antibiotic resistance crisis”, has been acknowledged by Scientific Societies and Public Health Agencies, and is now gathering an increasing attention from the Media and Governments. This article reviews the antibiotic-resistant pathogens which currently pose major problems in terms of clinical and epidemiological impact, and briefly discuss future perspective in this field.

scholarly journals Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 151
Author(s):  
Tatjana Kirtikliene ◽  
Aistė Mierauskaitė ◽  
Ilona Razmienė ◽  
Nomeda Kuisiene
Keyword(s):  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Essential Information ◽  
Acinetobacter Spp

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.

scholarly journals Combined Use of the Ab105-2фΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multiresistant Acinetobacter Baumannii

2019 ◽  
Author(s):  
Lucia Blasco ◽  
Anton Ambroa ◽  
Maria Lopez ◽  
Laura Fernandez-Garcia ◽  
Ines Bleriot ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Resistant Bacteria ◽  
Lytic Phage ◽  
Drug Resistant Bacteria ◽  
Multiresistant Strains

The global health emergency caused by multi-drug resistant bacteria has led to the search for and development of new antimicrobial agents. Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) showing antimicrobial activity against A.baumannii clinical strains (such as Ab177_GEIH-2000 which showed MICs to meropenem and imipenem of 32 µg/ml and 16 µg/ml, respectively as well as belonging to GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585). We then enhanced the time kill curves (in vitro) and in Galleria mellonella survival assays (in vivo) antimicrobial activity of the new lytic phage by combining it with carbapenem antibiotics (meropenem and imipenem). We observed in vitro, an antimicrobial synergistic effect (from 4 log to 7 log CFU/ml) with meropenem plus lytic phage in all combinations analysed (0.1, 1 and 10 MOI of Ab105-2phiΔCI mutant as well as 1/4 and 1/8 MIC of meropenem). Moreover, we had a decrease in bacterial growth of 8 log CFU/ml for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and of 4 log CFU/ml for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) in both MOI 1 and 10. These results were confirmed in in vivo (G. mellonella) obtaining a higher effectiveness in the combination of imipenem and Ab105-2phiΔCI mutant (P<0.05 by Log Rank-Matel Cox test). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to the antibiotics when used to combat multiresistant strains of Acinetobacter baumannii.

Antibiofilm action of Persea americana glycolic extract over Acinetobacter baumannii and absence of toxicity in Galleria mellonella

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sabrina Ferreira dos Santos Liberato ◽  
Mariana Raquel da Cruz Vegian ◽  
Amjad Abu Hasna ◽  
Janaína Araújo de Alvarenga ◽  
Juliana Guimarães dos Santos ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Alternative Therapy ◽  
Multidrug Resistant ◽  
Persea Americana ◽  
Antibiofilm Activity ◽  
Survival Percentage ◽  
Low Toxicity ◽  
Resistant Strains ◽  
Invertebrate Model

Abstract Objectives This study aimed to evaluate the antibiofilm activity and toxicity of the glycolic extract of Persea americana “P. americana” over multidrug-resistant strains of Acinetobacter baumannii “A. baumannii” as alternative therapy to be investigated. Methods A bacterial inoculum of each bacterial strain (4a, 5a, 9a, 12a, ATCC 19606) of A. baumannii was prepared and adjusted by the spectrophotometer. The microdilution broth method was performed to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). P. americana glycolic extracts were obtained of the tree stalk and leaves. The biofilm viability was tested by MTT assay after 5 min exposure. The toxicity of the extracts was tested by invertebrate model Galleria mellonella. The data were analyzed by ANOVA, Tukey test and log-rank method (α=0.05). Results The extract showed an inhibitory and bactericidal action over all the tested strains with the lowest MIC value observed for the reference strain (3.12 mg/mL). The extract did not demonstrate toxicity in any of the tested concentrations (12.5, 25 and 50 mg/mL) in Galleria mellonella larvae, with a survival percentage above 80% after 168 h. Conclusions The glycolic extract of P. americana has microbicidal and antibiofilm activity on multidrug-resistant clinical strains of A. baumannii and showed low toxicity for the invertebrate model G. mellonella.

Antibacterial and Antibiofilm Effects of Synbiotics against Multidrug-Resistant bacteria: Acinetobacter baumannii and Enterococcus faecalis

2020 ◽  
Author(s):  
Niki Laal-Kargar ◽  
Samaneh Dolatabadi ◽  
Mahnaz Mohtashami
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Antibiofilm Activity ◽  
Drug Resistant ◽  
Study Support ◽  
And Control

Abstract Background: Acinetobacter baumannii and Enterocoocus faecalis increase their resistance against antibiotic by producing biofilm. Antibiotic resistance has become a massive public health threat that require novel effective antibacterial and antibiofilm alternatives. The use of probiotics is interested to prevent and control certain infections. The objective of this study was to investigate the antibacterial and antibiofilm property of probiotics and synbiotics against multidrug-resistant A. baumannii and E. faecalis. Methods: The antimicrobial and the antibiofilm activities of cell- free supernatants of four strains of Lactobacillus against 20 clinical multi-drug resistant (MDR) isolates of Acinetobacter baumannii and Enterocoocus faecalis were determined in the presence of 0.3% of sorbitol, raffinose, citrate, trehalose, inulin, and riboflavin using well diffusion agar and micro-dilution method. Results: The cell- free supernatant of L. rhamnosus with citrate and trehalose showed the best antibacterial activity against MDR A. baumannii (28.8±2.1mm, 1.128 μL/mL), and L. rhamnosus with all of prebiotics against MDR E. faecalis (29.8±0 mm, 1.128 μL/mL) compare to probiotic alone. The prebiotics could improve the inhibitory effect of probiotics against the Gram-negative A. baumannii higher than Gram-positive E. faecalis. Biofilm formation was reduced in both pathogens in presence of synbiotics. L. plantarum with riboflavin and L. rhamnosus with or without inulin potently inhibits E. faecalis (50±0.86%) and A. baumannii (75±6.5%) biofilm formation, respectively. Conclusions: The results of current study support the antibiofilm activity of metabolites produced by synbiotics, and suggest their use as suitable adjuvants as well as biocontrol agents for treatment.

scholarly journals K2 Capsule Depolymerase Is Highly Stable, Is Refractory to Resistance, and Protects Larvae and Mice from Acinetobacter baumannii Sepsis

2019 ◽  
Vol 85 (17) ◽  
Author(s):  
Hugo Oliveira ◽  
Ana Mendes ◽  
Alexandra G. Fraga ◽  
Alice Ferreira ◽  
Andreia I. Pimenta ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Host Immune System ◽  
Dependent Manner ◽  
Bacterial Cells ◽  
Capsular Type ◽  
Nosocomial Pathogen ◽  
Content Type

ABSTRACT Acinetobacter baumannii is emerging as a major nosocomial pathogen in intensive care units. The bacterial capsules are considered major virulence factors, and the particular A. baumannii capsular type K2 has been associated with high antibiotic resistance. In this study, we identified a K2 capsule-specific depolymerase in a bacteriophage tail spike C terminus, a fragment that was heterologously expressed, and its antivirulence properties were assessed by in vivo experiments. The K2 depolymerase is active under a broad range of environmental conditions and is highly thermostable, with a melting point (Tm) at 67°C. In the caterpillar larva model, the K2 depolymerase protects larvae from bacterial infections, using either pretreatments or with single-enzyme injection after bacterial challenge, in a dose-dependent manner. In a mouse sepsis model, a single K2 depolymerase intraperitoneal injection of 50 μg is able to protect 60% of mice from an otherwise deadly infection, with a significant reduction in the proinflammatory cytokine profile. We showed that the enzyme makes bacterial cells fully susceptible to the host complement system killing effect. Moreover, the K2 depolymerase is highly refractory to resistance development, which makes these bacteriophage-derived capsular depolymerases useful antivirulence agents against multidrug-resistant A. baumannii infections. IMPORTANCE Acinetobacter baumannii is an important nosocomial pathogen resistant to many, and sometimes all, antibiotics. The A. baumannii K2 capsular type has been associated with elevated antibiotic resistance. The capsular depolymerase characterized here fits the new trend of alternative antibacterial agents needed against multidrug-resistant pathogens. They are highly specific, stable, and refractory to resistance, as they do not kill bacteria per se; instead, they remove bacterial surface polysaccharides, which diminish the bacterial virulence and expose them to the host immune system.

Simultaneous Antibacterial and Antibiofilm Activities of three Types of Silver Nanoparticles against Human Bacterial Pathogens.

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Suhad Hadi Mohammed ◽  
Maysaa Saleh Mahdi ◽  
Abbas Matrood Bashi ◽  
Mohanad Mohsin Ahmed
Keyword(s):  
Silver Nanoparticles ◽  
Biofilm Formation ◽  
Bacterial Infections ◽  
Significant Inhibition ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Antibiofilm Activity ◽  
Bacterial Cells ◽  
Dual Effect ◽  
Low Concentration

Emergence of antibiotic resistant bacteria result in an approximately 550,000 deaths from bacterial infections annually. Several studies reported interesting antibacterial and anti-biofilm activities of silver nanoparticles synthesized by different physical, chemical and biological methods as an alternative to antibiotics. However, the resultant nanoparticles were varying in size, shape, and had different antibacterial and antibiofilm activities with different concentrations. Moreover, previous studies had investigated the antibacterial and antibiofilm activities in separate protocols and didn’t investigate the real-time or dual effect of silver nanoparticles on both planktonic and sessile cells within single protocol. This study aimed to synthesize silver nanoparticles through three methods and analyzing the simultaneous antibacterial and antibiofilm activities against planktonic and sessile bacterial cells. Three methods were applied to analyze silver nanoparticles and used to investigate the dual effect against bacterial biomass and biofilm formation. The results showed that synthesized silver nanoparticles cause significant inhibition to bacterial cell biomass and bacterial biofilm formation when compared with controls at low concentration. Significant Higher antibiofilm activity than antibacterial activity was observed at very low concentration (0.0125 µg/ ml). The antibacterial and antibiofilm activity do not differ according to the type of bacteria. Whereas, the antibacterial effect differs significantly according to the methods of silver nanoparticles synthesis.

scholarly journals Analysis of Influencing Factors and Predictive Models of Multidrug-resistant Bacterial Infection in Severe Patients

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Xianhui Wang
Keyword(s):  
Influencing Factors ◽  
Bacterial Infections ◽  
Preventive Measures ◽  
Severe Disease ◽  
Risk Groups ◽  
The Elderly ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

Objective: To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model. Methods: 207 infected patients in our hospital from 2018 to May 2020 were selected for the study, of which 73 carried drug-resistant bacteria. Results: The risk factor network of people infected with multi-drug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria, and the interaction between risk factors of the former is stronger. Conclusion: Antibiotics must be used appropriately after surgery. When the elderly was abnormal in indicators such as fever and procalcitonin in the ward, they should be considered as high-risk groups of MDRO infection. They need special care and preventive measures.

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