scholarly journals Increased capsule thickness and hyper-motility are traits of carbapenem-resistant Acinetobacter baumannii ST3 strains causing fulminant infection

2021 ◽  
Author(s):  
Nadya Rakovitsky ◽  
Jonathan Lellouche ◽  
Debby Ben David ◽  
Sammy Frenk ◽  
Polet Elmalih ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Galleria Mellonella ◽  
Phylogenetic Analyses ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
World Health ◽  
Extracellular Polysaccharides ◽  
Clonal Type

Abstract Acinetobacter baumannii is a successful nosocomial pathogen, causing severe, life-threatening infections in hospitalized patients, including pneumonia and bloodstream infections. The spread of CRAB (carbapenem-resistance Acinetobacter baumannii) strains is a major world-health threat. The successful spread of CRAB is mostly due to it's highly plasticity genome. Although some virulence factors associated with CRAB have been uncovered, many mechanisms contributing to its success are not fully understood. Here we describe strains of CRAB that were isolated from fulminant cases in two hospitals in Israel. These isolates show a rare, hyper mucoid (HM) phenotype and were investigated using phenotypic assays, comparative genomics and in vivo Galleria Mellonella model. The three isolates belonged to the ST3 international clonal type and closely related to each-other as shown by Fourier Transform Infrared Spectroscopy (FTIR) and phylogenetic analyses. These isolates possessed thickened capsules and dense filamentous extracellular polysaccharides (EPS) matrix as shown by transmission electron microscopy (TEM), and overexpress capsule polysaccharide synthesis pathway-related wzc gene. The HM isolates possessed a unique combination of virulence genes involved in iron metabolism, protein secretion, adherence and membrane glycosylation. HM strains were more virulent than control strains in two G. mellonella infection models. In conclusion, our findings demonstrated several virulence factors, all present in three CRAB isolates with rare hyper mucoid phenotypes.

scholarly journals Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Atp Synthesis ◽  
Bloodstream Infections ◽  
Model Systems ◽  
Phenotypic Traits ◽  
Virulence Determinants ◽  
Expression Of Genes

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

scholarly journals Effects of Saline, an Ambient Acidic Environment, and Sodium Salicylate on OXA-Mediated Carbapenem Resistance in Acinetobacter baumannii: TABLE 1

2016 ◽  
Vol 60 (6) ◽  
pp. 3415-3418 ◽  
Author(s):  
Esther Zander ◽  
Harald Seifert ◽  
Paul G. Higgins
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
Sodium Salicylate ◽  
Carbapenem Resistance ◽  
Low Ph ◽  
Wild Type ◽  
Experimental Conditions ◽  
Content Type ◽  
Reference Strains

Different physiological conditions, such as NaCl, low pH, and sodium salicylate, have been shown to affect antibiotic resistance determinants inAcinetobacter baumanniiisolates. Therefore, the aim of this study was to investigate the effects of NaCl, sodium salicylate, and low pH on the susceptibility ofA. baumanniito carbapenem. We cloned genes encoding oxacillinases (OXA) of different subclasses, with their associated promoters, from carbapenem-resistantA. baumanniiisolates into the same vector and transferred them to theA. baumanniireference strains ATCC 19606 and ATCC 17978. Carbapenem MICs were determined at least in triplicate by agar dilution under standard conditions, as well as in the presence of 200 mM NaCl or 16 mM sodium salicylate, or at pH 5.8. OXA-58-like gene expression was determined by reverse transcription-quantitative PCR (qRT-PCR). Under some experimental conditions, significant MIC reductions were shown for some transformants but not for others. Only in one instance were all transformants harboring the same OXA affected by the same condition: at pH 5.8, the imipenem and meropenem MICs for strains expressing OXA-58-like enzymes decreased from a resistant level (32 to 64 mg/liter) to an intermediate-susceptible level (8 mg/liter). However,blaOXA-58-likegene expression remained the same. MICs for both wild-type reference strains were not affected by the conditions tested. Our results indicate that the effects of the experimental conditions tested on OXAin vivoare mostly strain dependent. MICs were not reduced to wild-type levels, suggesting that the conditions tested do not lead to complete OXA inhibition in the bacterial cell.

scholarly journals In VitroandIn VivoAntimicrobial Activities of Gallium Nitrate against Multidrug-Resistant Acinetobacter baumannii

2012 ◽  
Vol 56 (11) ◽  
pp. 5961-5970 ◽  
Author(s):  
Luísa C. S. Antunes ◽  
Francesco Imperi ◽  
Fabrizia Minandri ◽  
Paolo Visca
Keyword(s):  
Human Serum ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Therapeutic Potential ◽  
Survival Rates ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Gallium Nitrate ◽  
Content Type ◽  
Bacterial Physiology

ABSTRACTMultidrug-resistantAcinetobacter baumanniiposes a tremendous challenge to traditional antibiotic therapy. Due to the crucial role of iron in bacterial physiology and pathogenicity, we investigated iron metabolism as a possible target for anti-A. baumanniichemotherapy using gallium as an iron mimetic. Due to chemical similarity, gallium competes with iron for binding to several redox enzymes, thereby interfering with a number of essential biological reactions. We found that Ga(NO3)3, the active component of an FDA-approved drug (Ganite), inhibits the growth of a collection of 58A. baumanniistrains in both chemically defined medium and human serum, at concentrations ranging from 2 to 80 μM and from 4 to 64 μM, respectively. Ga(NO3)3delayed the entry ofA. baumanniiinto the exponential phase and drastically reduced bacterial growth rates. Ga(NO3)3activity was strongly dependent on iron availability in the culture medium, though the mechanism of growth inhibition was independent of dysregulation of gene expression controlled by the ferric uptake regulator Fur. Ga(NO3)3also protectedGalleria mellonellalarvae from lethalA. baumanniiinfection, with survival rates of ≥75%. At therapeutic concentrations for humans (28 μM plasma levels), Ga(NO3)3inhibited the growth in human serum of 76% of the multidrug-resistantA. baumanniiisolates tested by ≥90%, raising expectations on the therapeutic potential of gallium for the treatment ofA. baumanniibloodstream infections. Ga(NO3)3also showed strong synergism with colistin, suggesting that a colistin-gallium combination holds promise as a last-resort therapy for infections caused by pan-resistantA. baumannii.

Emergence of Carbapenem Resistance inAcinetobacter baumanniiRecovered From Blood Cultures in Australia

2006 ◽  
Vol 27 (7) ◽  
pp. 759-761 ◽  
Author(s):  
Anton Y. Peleg ◽  
Clare Franklin ◽  
Jan M. Bell ◽  
Denis W. Spelman
Keyword(s):  
Acinetobacter Baumannii ◽  
Linear Trend ◽  
Carbapenem Resistance ◽  
Blood Cultures ◽  
Clonal Type ◽  
Carbapenem Resistant ◽  
Genes Encoding ◽  
Blood Specimens

We describe the first emergence of carbapenem-resistantAcinetobacter baumanniiin Australia. NinetyA. baumanniiisolates recovered from cultures of blood specimens from 69 patients were analyzed. Overall, 58 isolates (64%) were resistant to meropenem. The χ2test for linear trend revealed that emergence of carbapenem resistance was statistically significant during the 32-month study period. Selected isolates were of the same clonal type, and no genes encoding carbapenemases were identified.

In vivo activity of daptomycin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection

2015 ◽  
Vol 45 (2) ◽  
pp. 188-191 ◽  
Author(s):  
Haifei Yang ◽  
Guosheng Chen ◽  
Lifen Hu ◽  
Yanyan Liu ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella

scholarly journals Antibiotics Act with vB_AbaP_AGC01 Phage against Acinetobacter baumannii in Human Heat-Inactivated Plasma Blood and Galleria mellonella Models

2020 ◽  
Vol 21 (12) ◽  
pp. 4390
Author(s):  
Bartłomiej Grygorcewicz ◽  
Marta Roszak ◽  
Piotr Golec ◽  
Daria Śleboda-Taront ◽  
Natalia Łubowska ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Phage Therapy ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Bacterial Species ◽  
Larval Survival ◽  
Broad Host Range ◽  
Phenotypic Analysis ◽  
In Vivo Models

Increasing multidrug resistance has led to renewed interest in phage-based therapy. A combination of the bacteriophages and antibiotics presents a promising approach enhancing the phage therapy effectiveness. First, phage candidates for therapy should be deeply characterized. Here we characterize the bacteriophage vB_AbaP_AGC01 that poses antibacterial activity against clinical Acinetobacter baumannii strains. Moreover, besides genomic and phenotypic analysis our study aims to analyze phage–antibiotic combination effectiveness with the use of ex vivo and in vivo models. The phage AGC01 efficiently adsorbs to A. baumannii cells and possesses a bacteriolytic lifecycle resulting in high production of progeny phages (317 ± 20 PFU × cell−1). The broad host range (50.27%, 93 out of 185 strains) against A. baumannii isolates and the inability of AGC01 to infect other bacterial species show its high specificity. Genomic analysis revealed a high similarity of the AGC01 genome sequence with that of the Friunavirus genus from a subfamily of Autographivirinae. The AGC01 is able to significantly reduce the A. baumannii cell count in a human heat-inactivated plasma blood model (HIP-B), both alone and in combination with antibiotics (gentamicin (GEN), ciprofloxacin (CIP), and meropenem (MER)). The synergistic action was observed when a combination of phage treatment with CIP or MER was used. The antimicrobial activity of AGC01 and phage-antibiotic combinations was confirmed using an in vivo larva model. This study shows the greatest increase in survival of G. mellonella larvae when the combination of phage (MOI = 1) and MER was used, which increased larval survival from 35% to 77%. Hence, AGC01 represents a novel candidate for phage therapy. Additionally, our study suggests that phages and antibiotics can act synergistically for greater antimicrobial effect when used as combination therapy.

scholarly journals Investigation of Novel pmrB and eptA Mutations in Isogenic Acinetobacter baumannii Isolates Associated with Colistin Resistance and Increased Virulence In Vivo

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Stefanie Gerson ◽  
Jonathan W. Betts ◽  
Kai Lucaßen ◽  
Carolina Silva Nodari ◽  
Julia Wille ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Lipid A ◽  
Galleria Mellonella ◽  
Resistance Mechanism ◽  
Resistant Isolate ◽  
Infection Model ◽  
Colistin Resistance ◽  
Strain Specificity ◽  
Content Type

ABSTRACT Colistin resistance in Acinetobacter baumannii is of great concern and is a threat to human health. In this study, we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, and ΔL9-G12). Increased expression of pmrC was shown by semi-quantitative reverse transcription-PCR (qRT-PCR) for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion ΔL9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain specific.

scholarly journals Impact of Carbapenem Resistance and Receipt of Active Antimicrobial Therapy on Clinical Outcomes of Acinetobacter baumannii Bloodstream Infections

2011 ◽  
Vol 55 (10) ◽  
pp. 4844-4849 ◽  
Author(s):  
John S. Esterly ◽  
Milena Griffith ◽  
Chao Qi ◽  
Michael Malczynski ◽  
Michael J. Postelnick ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Therapy ◽  
Active Agent ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Chronically Ill ◽  
Cox Proportional Hazards Model ◽  
Bivariate Analysis ◽  
Content Type

ABSTRACTNosocomialAcinetobacter baumanniibloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance inA. baumanniiand patient outcomes remains unclear. A retrospective cohort study was conducted on patients withA. baumanniibacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistantA. baumannii(CNRAB) and carbapenem-resistantA. baumannii(CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P< 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P= 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5;P< 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%;P= 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P= 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

scholarly journals Role of Acinetobactin-Mediated Iron Acquisition Functions in the Interaction of Acinetobacter baumannii Strain ATCC 19606Twith Human Lung Epithelial Cells, Galleria mellonella Caterpillars, and Mice

2012 ◽  
Vol 80 (3) ◽  
pp. 1015-1024 ◽  
Author(s):  
Jennifer A. Gaddy ◽  
Brock A. Arivett ◽  
Michael J. McConnell ◽  
Rafael López-Rojas ◽  
Jerónimo Pachón ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Iron Acquisition ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Content Type ◽  
Alveolar Epithelial

Acinetobacter baumannii, which causes serious infections in immunocompromised patients, expresses high-affinity iron acquisition functions needed for growth under iron-limiting laboratory conditions. In this study, we determined that the initial interaction of the ATCC 19606Ttype strain with A549 human alveolar epithelial cells is independent of the production of BasD and BauA, proteins needed for acinetobactin biosynthesis and transport, respectively. In contrast, these proteins are required for this strain to persist within epithelial cells and cause their apoptotic death. Infection assays usingGalleria mellonellalarvae showed that impairment of acinetobactin biosynthesis and transport functions significantly reduces the ability of ATCC 19606Tcells to persist and kill this host, a defect that was corrected by adding inorganic iron to the inocula. The results obtained with theseex vivoandin vivoapproaches were validated using a mouse sepsis model, which showed that expression of the acinetobactin-mediated iron acquisition system is critical for ATCC 19606Tto establish an infection and kill this vertebrate host. These observations demonstrate that the virulence of the ATCC 19606Tstrain depends on the expression of a fully active acinetobactin-mediated system. Interestingly, the three models also showed that impairment of BasD production results in an intermediate virulence phenotype compared to those of the parental strain and the BauA mutant. This observation suggests that acinetobactin intermediates or precursors play a virulence role, although their contribution to iron acquisition is less relevant than that of mature acinetobactin.

scholarly journals The antimicrobial activity of silver acetate against Acinetobacter baumannii in a Galleria mellonella infection model

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11196
Author(s):  
Eden Mannix-Fisher ◽  
Samantha McLean
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Galleria Mellonella ◽  
World Health Organisation ◽  
World Health ◽  
Infection Model ◽  
Silver Acetate ◽  
Selective Toxicity ◽  
Carbapenem Resistant

Background The increasing prevalence of bacterial infections that are resistant to antibiotic treatment has caused the scientific and medical communities to look for alternate remedies aimed at prevention and treatment. In addition to researching novel antimicrobials, there has also been much interest in revisiting some of the earliest therapies used by man. One such antimicrobial is silver; its use stretches back to the ancient Greeks but interest in its medicinal properties has increased in recent years due to the rise in antibiotic resistance. Currently antimicrobial silver is found in everything from lunch boxes to medical device implants. Though much is claimed about the antimicrobial efficacy of silver salts the research in this area is mixed. Methods Herein we investigated the efficacy of silver acetate against a carbapenem resistant strain of Acinetobacter baumannii to determine the in vitro activity of this silver salt against a World Health Organisation designated category I critical pathogen. Furthermore, we use the Galleria mellonella larvae model to assess toxicity of the compound and its efficacy in treating infections in a live host. Results We found that silver acetate can be delivered safely to Galleria at medically relevant and antimicrobial levels without detriment to the larvae and that administration of silver acetate to an infection model significantly improved survival. This demonstrates the selective toxicity of silver acetate for bacterial pathogens but also highlights the need for administration of well-defined doses of the antimicrobial to provide an efficacious treatment.

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