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Molecular Biology Reports Oct 2021Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality... (Review)
Review
Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality rate because strains resistant to antimicrobial agents are a major challenge for physicians and healthcare workers regarding the eradication of either hospital or community-based infections. These strains with emerging resistance are a serious issue for patients in the intensive care unit (ICU). Antibiotic resistance has increased because of the acquirement of mobile genetic elements such as transposons, plasmids, and integrons and causes the prevalence of multidrug resistance strains (MDR). In addition, an increase in carbapenem resistance, which is used as last line antibiotic treatment to eliminate infections with multidrug-resistant Gram-negative bacteria, is a major concern. Carbapenems resistant A. baumannii (CR-Ab) is a worldwide problem. Because these strains are often resistant to all other commonly used antibiotics. Therefore, pathogenic multi-drug resistance A. baumannii (MDR-Ab) associated infections become hard to eradicate. Plasmid-mediated resistance causes outbreaks of extensive drug-resistant. A. baumannii (XDR-Ab). In addition, recent outbreaks relating to livestock and community settings illustrate the existence of large MDR-Ab strain reservoirs within and outside hospital settings. The purpose of this review, proper monitoring, prevention, and treatment are required to control (XDR-Ab) infections. Attachment, the formation of biofilms and the secretion of toxins, and low activation of inflammatory responses are mechanisms used by pathogenic A. baumannii strain. This review will discuss some aspects associated with antibiotics resistance in A. baumannii as well as cover briefly phage therapy as an alternative therapeutic treatment.
Topics: Acinetobacter baumannii; Biofilms; Drug Resistance, Multiple, Bacterial; Hospitals; Host-Pathogen Interactions; Humans; Quorum Sensing; Virulence
PubMed: 34460060
DOI: 10.1007/s11033-021-06690-6 -
Science (New York, N.Y.) Aug 2023Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect...
Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors. We characterized the functionality of the biosensors in vitro with coculture assays and then validated them in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observed horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. This cellular assay for targeted, CRISPR-discriminated horizontal gene transfer (CATCH) enables the biodetection of specific cell-free DNA.
Topics: Animals; Humans; Mice; Colorectal Neoplasms; DNA, Neoplasm; Mutation; Acinetobacter; Cell-Free Nucleic Acids; Bioengineering; Biosensing Techniques
PubMed: 37561843
DOI: 10.1126/science.adf3974 -
Microbiological Research Jun 2021The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in... (Review)
Review
The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Biofilms; Cross Infection; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Host-Pathogen Interactions; Humans; Sepsis; Virulence Factors
PubMed: 33618061
DOI: 10.1016/j.micres.2021.126722 -
Viruses Mar 2023() is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With the increase of drug-resistant infections, it is urgent to... (Review)
Review
() is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With the increase of drug-resistant infections, it is urgent to find some new treatment strategies, such as phage therapy. In this paper, we described the different drug resistances of and some basic properties of phages, analyzed the interaction between phages and their hosts, and focused on phage therapies. Finally, we discussed the chance and challenge of phage therapy. This paper aims to provide a more comprehensive understanding of phages and theoretical support for the clinical application of phages.
Topics: Bacteriophages; Acinetobacter baumannii; Anti-Bacterial Agents
PubMed: 36992382
DOI: 10.3390/v15030673 -
Biomolecules May 2020is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting... (Review)
Review
is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by . We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in clinical isolates.
Topics: Acinetobacter baumannii; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Enzyme Inhibitors; beta-Lactamases
PubMed: 32384624
DOI: 10.3390/biom10050720 -
Clinical Infectious Diseases : An... May 2023Acinetobacter baumannii-calcoaceticus complex is the most commonly identified species in the genus Acinetobacter and it accounts for a large percentage of nosocomial...
Acinetobacter baumannii-calcoaceticus complex is the most commonly identified species in the genus Acinetobacter and it accounts for a large percentage of nosocomial infections, including bacteremia, pneumonia, and infections of the skin and urinary tract. A few key clones of A. baumannii-calcoaceticus are currently responsible for the dissemination of these organisms worldwide. Unfortunately, multidrug resistance is a common trait among these clones due to their unrivalled adaptive nature. A. baumannii-calcoaceticus isolates can accumulate resistance traits by a plethora of mechanisms, including horizontal gene transfer, natural transformation, acquisition of mutations, and mobilization of genetic elements that modulate expression of intrinsic and acquired genes.
Topics: Humans; Acinetobacter baumannii; Anti-Bacterial Agents; Acinetobacter calcoaceticus; Acinetobacter Infections; Acinetobacter; Bacteremia; Drug Resistance, Multiple, Bacterial
PubMed: 37125466
DOI: 10.1093/cid/ciad109 -
Microbiology Spectrum Oct 2021Tigecycline is regarded as a last-resort treatment for multidrug-resistant Acinetobacter baumannii. However, tigecycline resistance in A. baumannii has increased...
Tigecycline is regarded as a last-resort treatment for multidrug-resistant Acinetobacter baumannii. However, tigecycline resistance in A. baumannii has increased worldwide. In this study, we investigated tigecycline heteroresistance in A. baumannii isolates from South Korea. Antibiotic susceptibility testing was performed on 323 nonduplicated A. baumannii isolates. Among 260 and 37 tigecycline-susceptible and -intermediate-resistant A. baumannii isolates, 146 (56.2%) and 22 (59.5%) isolates were identified as heteroresistant to tigecycline through a disk diffusion assay and population analysis profiling. For selected isolates, an time-kill assay was performed, and survival rates were measured after preincubation with diverse concentrations of tigecycline. Heteroresistant isolates showed regrowth after 12 h of 2× MIC of tigecycline treatment, and resistant subpopulations were selected by preexposure to tigecycline. Furthermore, genetic alterations in , and were assessed, and the relative mRNA expression levels of and were compared. The tigecycline resistance in subpopulations might be due to the insertion of IS in , leading to the overexpression of the AdeABC efflux pump. However, the tigecycline resistance of subpopulations was not stable during serial passages in antibiotic-free medium. The reversion of tigecycline susceptibility by antibiotic-free passages might occur by additional insertions of IS in and nucleotide alterations in in some mutants. Tigecycline heteroresistance is prevalent in A. baumannii isolates, which results in treatment failure. Tigecycline resistance is mainly due to the overexpression of the AdeABC efflux pump, which is associated with genetic mutations, but this resistance could be reversed into susceptibility by additional mutations in antibiotic-free environments. The evidence that antibiotic heteroresistance is responsible for treatment failure in clinical settings is increasing. Thus, detection and characterization of heteroresistance would be important for appropriate therapeutic guidance to treat bacterial infections. However, data on tigecycline heteroresistance in Gram-negative bacteria is currently limited, although tigecycline is regarded as a last-line antibiotic against infections caused by antibiotic-resistant pathogens. In this study, we investigated the tigecycline heteroresistance in Acinetobacter baumannii, which has been listed by the WHO as a priority for research and development of new antibiotics. We found very high prevalence of tigecycline-heteroresistant A. baumannii clinical isolates, which may result in treatment failure due to the selection of resistant subpopulations. We also identified the main resistance mechanism in tigecycline-resistant subpopulations, that is, upregulation of AdeABC efflux pumps due to IS insertion in
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Membrane Transport Proteins; RNA, Messenger; Ribosomal Proteins; Tigecycline
PubMed: 34523993
DOI: 10.1128/Spectrum.01010-21 -
Journal of Biomedical Science Jan 2020Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening... (Review)
Review
Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening Gram-negative bacteria (GNB). Outer membrane protein A (OmpA), a major component of outer membrane proteins (OMPs) in GNB, is a key virulence factor which mediates bacterial biofilm formation, eukaryotic cell infection, antibiotic resistance and immunomodulation. The characteristics of OmpA in Escherichia coli (E. coli) have been extensively studied since 1974, but only in recent years researchers started to clarify the functions of OmpA in A. baumannii. In this review, we summarized the structure and functions of OmpA in A. baumannii (AbOmpA), collected novel therapeutic strategies against it for treating A. baumannii infection, and emphasized the feasibility of using AbOmpA as a potential therapeutic target.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Bacterial Outer Membrane Proteins; Humans
PubMed: 31954394
DOI: 10.1186/s12929-020-0617-7 -
Cell Host & Microbe Jul 2022Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here,...
Acinetobacter baumannii is a leading cause of hospital-acquired infections, where outbreaks are driven by its ability to persist on surfaces in a desiccated state. Here, we show that A. baumannii causes more virulent pneumonia following desiccation and profile the genetic requirements for desiccation. We find that desiccation tolerance is enhanced upon the disruption of Lon protease, which targets unfolded and aggregated proteins for degradation. Notably, two bacterial hydrophilins, DtpA and DtpB, are transcriptionally upregulated in Δlon via the two-component regulator, BfmR. These proteins, both hydrophilic and intrinsically disordered, promote desiccation tolerance in A. baumannii. Additionally, recombinant DtpA protects purified enzymes from inactivation and improves the desiccation tolerance of a probiotic bacterium when heterologously expressed. These results demonstrate a connection between environmental persistence and pathogenicity in A. baumannii, provide insight into the mechanisms of extreme desiccation tolerance, and reveal potential applications for bacterial hydrophilins in the preservation of protein- and live bacteria-based pharmaceuticals.
Topics: Acinetobacter baumannii; Bacterial Proteins; Desiccation; Pentetic Acid; Virulence
PubMed: 35413266
DOI: 10.1016/j.chom.2022.03.019 -
Microbes and Infection 2021
Topics: Acinetobacter baumannii; Klebsiella pneumoniae
PubMed: 33892150
DOI: 10.1016/j.micinf.2021.104830