scholarly journals Antibiotic Resistance Profiles, Molecular Mechanisms and Innovative Treatment Strategies of Acinetobacter baumannii

2020 ◽  
Vol 8 (6) ◽  
pp. 935 ◽  
Author(s):  
Corneliu Ovidiu Vrancianu ◽  
Irina Gheorghe ◽  
Ilda Barbu Czobor ◽  
Mariana Carmen Chifiriuc
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Negative Bacterium ◽  
Innovative Strategies ◽  
Industry Environment ◽  
Underlying Mechanisms

Antibiotic resistance is one of the biggest challenges for the clinical sector and industry, environment and societal development. One of the most important pathogens responsible for severe nosocomial infections is Acinetobacter baumannii, a Gram-negative bacterium from the Moraxellaceae family, due to its various resistance mechanisms, such as the β-lactamases production, efflux pumps, decreased membrane permeability and altered target site of the antibiotic. The enormous adaptive capacity of A. baumannii and the acquisition and transfer of antibiotic resistance determinants contribute to the ineffectiveness of most current therapeutic strategies, including last-line or combined antibiotic therapy. In this review, we will present an update of the antibiotic resistance profiles and underlying mechanisms in A. baumannii and the current progress in developing innovative strategies for combating multidrug-resistant A. baumannii (MDRAB) infections.

scholarly journals Programmable Base Editing in Mycobacterium tuberculosis Using an Engineered CRISPR RNA-Guided Cytidine Deaminase

2021 ◽  
Vol 3 ◽  
Author(s):  
Xin-Yuan Ding ◽  
Si-Shang Li ◽  
Yi-Man Geng ◽  
Mei-Yi Yan ◽  
Guo-Bao Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Molecular Mechanisms ◽  
Cytidine Deaminase ◽  
Point Mutations ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Bacterial Physiology ◽  
Base Editing

Multidrug-resistant Mycobacterium tuberculosis (Mtb) infection seriously endangers global human health, creating an urgent need for new treatment strategies. Efficient genome editing tools can facilitate identification of key genes and pathways involved in bacterial physiology, pathogenesis, and drug resistance mechanisms, and thus contribute to the development of novel treatments for drug-resistant tuberculosis. Here, we report a two-plasmid system, MtbCBE, used to inactivate genes and introduce point mutations in Mtb. In this system, the assistant plasmid pRecX-NucSE107A expresses RecX and NucSE107A to repress RecA-dependent and NucS-dependent DNA repair systems, and the base editor plasmid pCBE expresses a fusion protein combining cytidine deaminase APOBEC1, Cas9 nickase (nCas9), and uracil DNA glycosylase inhibitor (UGI). Together, the two plasmids enabled efficient G:C to A:T base pair conversion at desired sites in the Mtb genome. The successful development of a base editing system will facilitate elucidation of the molecular mechanisms underlying Mtb pathogenesis and drug resistance and provide critical inspiration for the development of base editing tools in other microbes.

scholarly journals Complete Genome Sequence of Multidrug-ResistantPlesiomonas shigelloidesStrain MS-17-188

2018 ◽  
Vol 6 (18) ◽  
Author(s):  
Hossam Abdelhamed ◽  
Ozan Ozdemir ◽  
Hasan C. Tekedar ◽  
Mark A. Arick ◽  
Chuan-Yu Hsu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Plesiomonas Shigelloides ◽  
Content Type

ABSTRACTPlesiomonas shigelloidesis a Gram-negative bacterium isolated from diverse environments. Here, we describe the complete genome sequence of the multidrug-resistantP. shigelloidesstrain MS-17-188, isolated from a diseased catfish. Availability of this genome will be beneficial for characterizing the molecular mechanisms of antibiotic resistance in this strain.

scholarly journals Genomic analysis reveals high virulence and antibiotic resistance amongst phage susceptible Acinetobacter baumannii

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Udomluk Leungtongkam ◽  
Rapee Thummeepak ◽  
Thawatchai Kitti ◽  
Kannipa Tasanapak ◽  
Jintana Wongwigkarn ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Copper Tolerance ◽  
Virulence Determinants ◽  
Genome Sequences ◽  
High Virulence

Abstract In this study, we examined the association between antimicrobial resistance, CRISPR/Cas systems and virulence with phage susceptibility in Acinetobacter baumannii and investigated draft genomes of phage susceptible multidrug resistant A. baumannii strains from Thailand. We investigated 230 A. baumannii strains using 17 lytic A. baumannii phages and the phage susceptibility was 46.5% (107/230). Phage susceptibility was also associated with resistance to numerous antibiotics (p-value < 0.05). We also found association between biofilm formation and the presence of ompA gene among phage susceptible A. baumannii strains (p-value < 0.05). A. baumannii isolates carrying cas5 or combinations of two or three other cas genes, showed a significant increase in phage resistance. Whole-genome sequences of seven phage susceptible A. baumannii isolates revealed that six groups of antibiotic resistance genes were carried by all seven phage susceptible A. baumannii. All strains carried biofilm associated genes and two strains harbored complete prophages, acquired copper tolerance genes, and CRISPR-associated (cas) genes. In conclusion, our data exhibits an association between virulence determinants and biofilm formation among phage susceptible A. baumannii strains. These data help to understand the bacterial co-evolution with phages.

scholarly journals Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 148 ◽  
Author(s):  
Cuong Hoang Quoc ◽  
Thao Nguyen Thi Phuong ◽  
Hai Nguyen Duc ◽  
Trung Tran Le ◽  
Hang Tran Thi Thu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Demographic Data ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Background: Acinetobacter baumannii (Ab) is an opportunistic bacterial pathogen found in hospital-acquired infections including nosocomial pneumonia, especially multidrug-resistant Ab. This study aims to survey the drug resistance profiles of Ab isolated from patients in Thong Nhat Dong Nai General Hospital and assess the relationship between genotypes and antibiotic resistance; Methods: Ninety-seven Ab strains isolated from 340 lower respiratory tract specimens among pneumonia patients were used to screen the most common local carbapenemase genes. Antimicrobial susceptibility testing results and demographic data were collected and minimum inhibitory concentrations (MIC) of colistin were also determined; Results: Over 80% and 90% of Ab strains were determined as carbapenem-resistant and multidrug-resistant (MDR), respectively. Most of the strains carried carbapenemase genes, including blaOXA-51, blaOXA-23-like, blaOXA-58-like, and blaNDM-1, with proportions of 97 (100%), 76 (78.4%), 10 (10.3%), 6 (6.2%), respectively. Amongst these genes, blaOXA-23-like was the only gene which significantly influenced the resistance (p < 0.0001); and Conclusions: The severity of Ab antibiotic resistance is urgent and specifically related to carbapenemase encoding genes. Therefore, screening of MDR Ab and carbapenemase for better treatment options is necessary.

scholarly journals Biofilm Formation and Detection of Fluoroquinolone- and Carbapenem-Resistant Genes in Multidrug-Resistant Acinetobacter baumannii

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
María-Guadalupe Avila-Novoa ◽  
Oscar-Alberto Solís-Velázquez ◽  
Daniel-Eduardo Rangel-López ◽  
Jean-Pierre González-Gómez ◽  
Pedro-Javier Guerrero-Medina ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Low Grade ◽  
Carbapenem Resistant ◽  
Hospital Environments ◽  
Potential Association ◽  
Clinical Environments

Acinetobacter baumannii is an important opportunistic pathogen that shows resistance to cephalosporins, penicillins, carbapenems, fluoroquinolones, and aminoglycosides, the multiresistance being associated with its ability to form biofilms in clinical environments. The aim of this study was to determine biofilm formation and its potential association with genes involved in antibiotic resistance mechanisms of A. baumannii isolates of different clinical specimens. We demonstrated 100% of the A. baumannii isolates examined to be multidrug resistant (MDR), presenting a 73.3% susceptibility to cefepime and a 53.3% susceptibility to ciprofloxacin. All A. baumannii isolates were positive for blaOXA-51, 33.3% being positive for blaOXA-23 and ISAba1, and 73.3% being positive for gyrA. We found 86.6% of A. baumannii strains to be low-grade biofilm formers and 13.3% to be biofilm negative; culturing on Congo red agar (CRA) plates revealed that 73.3% of the A. baumannii isolates to be biofilm producers, while 26.6% were not. These properties, combined with the role of A. baumannii as a nosocomial pathogen, increase the probability of A. baumannii causing nosocomial infections and outbreaks as a complication during therapeutic treatments and emphasize the need to control A. baumannii biofilms in hospital environments.

scholarly journals Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 119 ◽  
Author(s):  
Carole Ayoub Moubareck ◽  
Dalal Hammoudi Halat
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Efflux Pump ◽  
Iron Acquisition ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Biofilm Production ◽  
Resistant Phenotype ◽  
Severe Infections ◽  
Hydrolyzing Enzymes

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

Proteomic Analyses Uncover the Mechanisms Underlying Antibiotic Resistance Differences among Three Acinetobacter baumannii Isolates

2016 ◽  
Vol 26 (6) ◽  
pp. 401-409 ◽  
Author(s):  
Junrui Wang ◽  
Junli Zhang ◽  
Quan Fu ◽  
Sufang Guo ◽  
La Ta ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Carbapenem Resistance ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Absolute Quantification ◽  
Functional Enrichment ◽  
Resistant Isolate ◽  
Gentamicin Resistance

This study aimed to investigate the molecular mechanisms underlying the antibiotic resistance difference among three <i>Acinetobacter baumannii</i> isolates. Fifty <i>A. baumannii</i> isolates were first subjected to an antimicrobial susceptibility test, then three isolates differing in antibiotic resistance were selected and subjected to iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics analysis. Differential proteins among the three <i>A. baumannii</i> isolates were further identified and subjected to gene ontology functional enrichment analysis. A resistant isolate (A1), a less resistant one (A8) and a susceptible one (A9) were selected. In total, there were 424 differentially expressed proteins (DEPs) between the A1 and A8 isolates, 1,992 DEPs between the A9 and A1 isolates, and 1,956 DEPs between the A8 and A9 isolates. The upregulation of I6TUC8 and Q0GA83 in the A1 and A8 isolates may be responsible for their higher resistance to ceftriaxone. The higher gentamicin resistance of <i>A. baumannii</i> isolates A1 and A8 when compared to A9 may be related to the higher expression levels of O05286 and D0CCK1, while the higher Q2FCY1 expression level may contribute more to strong gentamicin resistance in A1. The higher levels of L9LWL7, L9MDB0, K9C9W3, E2IGU7, B6E129, G8HYR7, D2XTB0 and D2XTB0 may be responsible for the higher carbapenem resistance of isolate A1 as compared to A8.

scholarly journals DNA Microarray for Genotyping Antibiotic Resistance Determinants in Acinetobacter baumannii Clinical Isolates

2013 ◽  
Vol 57 (10) ◽  
pp. 4761-4768 ◽  
Author(s):  
Simon Dally ◽  
Karin Lemuth ◽  
Martin Kaase ◽  
Steffen Rupp ◽  
Cornelius Knabbe ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Predictive Value ◽  
Handling Time ◽  
Multidrug Resistant ◽  
Testing System ◽  
Content Type ◽  
Resistance Determinants ◽  
Epidemiologic Surveillance ◽  
National Reference Center

ABSTRACTIn recent decades,Acinetobacter baumanniihas emerged as an organism of great concern due to its ability to accumulate antibiotic resistance. In order to improve the diagnosis of resistance determinants inA. baumanniiin terms of lead time and accuracy, we developed a microarray that can be used to detect 91 target sequences associated with antibiotic resistance within 4 h from bacterial culture to result. The array was validated with 60 multidrug-resistant strains ofA. baumanniiin a blinded, prospective study. The results were compared to phenotype results determined by the automated susceptibility testing system VITEK2. Antibiotics considered were piperacillin-tazobactam, ceftazidime, imipenem, meropenem, trimethoprim-sulfamethoxazole, amikacin, gentamicin, tobramycin, ciprofloxacin, and tigecycline. The average positive predictive value, negative predictive value, sensitivity, and specificity were 98, 98, 99, and 94%, respectively. For carbapenemase genes, the array results were compared to singleplex PCR results provided by the German National Reference Center for Gram-Negative Pathogens, and results were in complete concordance. The presented array is able to detect all relevant resistance determinants ofA. baumanniiin parallel. The short handling time of 4 h from culture to result helps to provide fast results in order to initiate adequate anti-infective therapy for critically ill patients. Another application would be data acquisition for epidemiologic surveillance.

scholarly journals Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

2018 ◽  
Author(s):  
Yousif Mohammed Alfatih ◽  
Abeer Babiker Idris ◽  
Hadeel Gassim Hassan ◽  
Eman O M Nour ◽  
Nihad M A Elhaj ◽  
...  
Keyword(s):  
16S Rrna ◽  
Molecular Mechanisms ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
World Health ◽  
Bacterial Disease ◽  
Global Public Health ◽  
Mdr Tb ◽  
Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

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