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

2020 ◽  
Author(s):  
Jasmine Martinez ◽  
Chelsea Razo-Gutierrez ◽  
Casin Le ◽  
Robert Courville ◽  
Camila Pimentel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Respiratory Infections ◽  
Atp Synthesis ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Model Systems ◽  
Phenotypic Traits ◽  
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, urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, a common complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, it is necessary to identify signals, such as exposure to cerebrospinal fluid (CSF), that trigger expression of virulence factors that are associated with the successful establishment and progress of this infection. 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 virulence as determined in various model systems. Furthermore, although CSF’s presence did not enhance bacterial growth, it was associated with an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery. Experiments to identify the active CSF component pointed to human serum albumin (HSA).ImportanceAcinetobacter baumannii, notorious for its multidrug resistant phenotype, overcomes nutrient deprived and desiccated conditions through its metabolic flexibility, pathogenic and physiological adaptability. Although this pathogen is commonly associated with respiratory infections, there have been a considerable amount of cases of A. baumannii bacterial meningitis. These infections are usually post-neurological surgery complications associated with high mortality rates ranging from 40 to 70%. This work describes interactions that may occur during A. baumannii infection of human cerebrospinal fluid (CSF). A. baumannii’s displays capabilities to persist and thrive in a nutrient-limited environment, which also triggers the expression of virulence factors. This work also further explores A. baumannii’s utilization of an essential component within CSF to trigger enhanced expression of genes associated with its pathoadaptibility in this environment.

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 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.

scholarly journals Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 720 ◽  
Author(s):  
Maria Soledad Ramirez ◽  
Robert A. Bonomo ◽  
Marcelo E. Tolmasky
Keyword(s):  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Acquired Resistance ◽  
Clinical Manifestations ◽  
High Capacity ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Wound Infections ◽  
Extensively Drug Resistant

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii 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 A. baumannii 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. A. baumannii 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 A. baumannii 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 A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

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.

scholarly journals Bloodstream infections caused by ST2 Acinetobacter baumannii : Risk factors, antibiotic regimens, and virulence over 6 years period in China

2020 ◽  
Author(s):  
Kaihang Yu ◽  
Weiliang Zeng ◽  
Ye Xu ◽  
Wenli Liao ◽  
Wenya Xu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acinetobacter Baumannii ◽  
Bloodstream Infection ◽  
Bloodstream Infections ◽  
Tertiary Hospital ◽  
Multidrug Resistant ◽  
High Serum ◽  
Hospitalized Patients ◽  
Effective Treatment Option ◽  
Difficult Challenge

Abstract Background: Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in ChinaMethods: This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed. Results: A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2, a sequence type that has spread all over the world. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after positive blood culture, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline.Conclusions: BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option.

scholarly journals Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: A retrospective study in the Pediatric Intensive Care Unit

2020 ◽  
Author(s):  
Jingyi Shi ◽  
Ting Sun ◽  
Yun Cui ◽  
Chunxia Wang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Serum Level ◽  
Acinetobacter Baumannii ◽  
High Mortality ◽  
Pediatric Intensive Care ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
High Serum ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Overall Mortality

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors for MDR/XDR Acinetobacter baumannii infection and for overall mortality in this patient population. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Clinical presentations and outcome of the patients were analyzed. The primary outcome was overall mortality. Secondary outcomes included the 28-day mortality and the length of hospital stay. Results Of the 102 patients (63 males and 39 females; mean age: 51.79 months), the overall mortality rate was 29.41%. 18(17.64%) had bloodstream infections;4(3.92%) for which cerebrospinal fluid (CSF) cultures were positive; 14(13.73%) of them got positive cultures in aseptic fluid; 10 (9.8%) had central catheter-associated bloodstream infections; lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity 5.87%(2.43%, 8.93%) vs. 8.45%(4.51%, 14.61%), P =0.011), higher CD4 + T cell ratio (35.32% (29%, 47.81%) vs. 31.97% (20.52%, 38.22%), P = 0.045), and higher serum level of interlukin-6 (IL-6, 235.51(0.1, 4172.77) pg/ml vs. 0.1(0.1, 110.92) pg/ml, P = 0.028), interlukin-8 (IL-8, 22.73(3.14, 540.12) vs. 0.1(0.1, 25.85)pg/ml, P = 0.03) , and interlukin-10(10.82(0.1, 83.29)pg/ml vs. 6.05(0.1,21.81)pg/ml) were observed. Multivariate logistic analysis indicated that high serum level of BUN (RR, 1.216, 95%CI, 1.27-2.616; P = 0.001) and high serum level of Cr (RR, 1.823, 95%CI, 0.902-0.980；P=0.004,) were associated with high risk of overall mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR- Acinetobacter baumannii is an important opportunistic pathogen that causes nosocomial infection in PICU with a rather high mortality. The incidence increased in recent years, ineffective management, immune dysfunction, acute kidney injury contributed to the risk of death.

scholarly journals Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: A retrospective study in the Pediatric Intensive Care Unit

2020 ◽  
Author(s):  
Jingyi Shi ◽  
Ting Sun ◽  
Yun Cui ◽  
Chunxia Wang ◽  
Fei Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Acinetobacter Baumannii ◽  
High Mortality ◽  
Pediatric Patients ◽  
Pediatric Intensive Care ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Extensively Drug Resistant ◽  
Risk Of Mortality ◽  
Overall Mortality

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors for MDR/XDR Acinetobacter baumannii infection and for overall mortality in this patient population. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Results A total of 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 (61.8%) male in the case group. The overall mortality rate was 29.4% (30/102), while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2%±3.61% vs. 9.15%±6.21%, P =0.029), higher CD4+ T cell ratio (39.67%±12.18% vs. 32.66%±11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/ml vs. 0.1 (0.1, 22.99)pg/ml, P=0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890-0.981；P=0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425-870.574; p= 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality (29.4%). Bloodstream and central nervous infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.

scholarly journals Bloodstream infections caused by ST2 Acinetobacter baumannii: Risk factors, antibiotic regimens, and virulence over 6 years period in China

2020 ◽  
Author(s):  
Kaihang Yu ◽  
Weiliang Zeng ◽  
Ye Xu ◽  
Wenli Liao ◽  
Wenya Xu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acinetobacter Baumannii ◽  
Bloodstream Infection ◽  
Bloodstream Infections ◽  
Tertiary Hospital ◽  
Multidrug Resistant ◽  
High Serum ◽  
Hospitalized Patients ◽  
Effective Treatment Option ◽  
Difficult Challenge

Abstract Background: Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in ChinaMethods: This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed.Results: A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after bacteria isolation from blood, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline.Conclusions: BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option.

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