scholarly journals Three-Dimensional Human Skin Equivalent as a Tool To Study Acinetobacter baumannii Colonization

2012 ◽  
Vol 56 (5) ◽  
pp. 2459-2464 ◽  
Author(s):  
Anna de Breij ◽  
Elisabeth M. Haisma ◽  
Marion Rietveld ◽  
Abdelouahab El Ghalbzouri ◽  
Peterhans J. van den Broek ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Acinetobacter Baumannii ◽  
Bacterial Colonization ◽  
Three Dimensional ◽  
Skin Equivalent ◽  
Hospital Environment ◽  
Content Type ◽  
Acinetobacter Junii ◽  
Promising Tool ◽  
Skin Colonization

ABSTRACTAcinetobacter baumanniican colonize body surfaces of hospitalized patients. From these sites, invasion into the host and spread to other patients and the hospital environment may occur. The eradication of the organism from the patient's skin is an important infection control strategy during epidemic and endemic episodes. In this study, a three-dimensional (3D), air-exposed human epidermal skin equivalent was exploited to studyAcinetobacterskin colonization. We characterized the adherence ofA. baumanniiATCC 19606TandAcinetobacter juniiRUH2228Tto and biofilm formation on the skin equivalent and the responses to these bacteria. Furthermore, we assessed the ability of the disinfectant chlorhexidine to decolonize the skin equivalents. The results revealed that both strains replicated on the stratum corneum for up to 72 h but did not invade the epidermis.A. baumannii, in contrast toA. junii, formed large biofilms on the stratum corneum. Bacterial colonization did not affect keratinocyte activation, proliferation, or differentiation, nor did it induce a strong inflammatory response. Disinfection with chlorhexidine solution resulted in complete eradication ofA. baumanniifrom the skin, without detrimental effects. This 3D model is a promising tool to study skin colonization and to evaluate the effects of novel disinfectant and antimicrobial strategies.

scholarly journals Serum Albumin and Ca2+Are Natural Competence Inducers in the Human Pathogen Acinetobacter baumannii

2016 ◽  
Vol 60 (8) ◽  
pp. 4920-4929 ◽  
Author(s):  
German Matias Traglia ◽  
Brettni Quinn ◽  
Sareda T. J. Schramm ◽  
Alfonso Soler-Bistue ◽  
Maria Soledad Ramirez
Keyword(s):  
Acinetobacter Baumannii ◽  
Natural Transformation ◽  
Hospital Environment ◽  
Human Pathogen ◽  
Nosocomial Pathogen ◽  
Natural Competence ◽  
Exogenous Dna ◽  
Content Type ◽  
Resistance Determinants ◽  
Main Protein

ABSTRACTThe increasing frequency of bacteria showing antimicrobial resistance (AMR) raises the menace of entering into a postantibiotic era. Horizontal gene transfer (HGT) is one of the prime reasons for AMR acquisition.Acinetobacter baumanniiis a nosocomial pathogen with outstanding abilities to survive in the hospital environment and to acquire resistance determinants. Its capacity to incorporate exogenous DNA is a major source of AMR genes; however, few studies have addressed this subject. The transformation machinery as well as the factors that induce natural competence inA. baumanniiare unknown. In this study, we demonstrate that naturally competent strain A118 increases its natural transformation frequency upon the addition of Ca2+or albumin. We show thatcomEAandpilQare involved in this process since their expression levels are increased upon the addition of these compounds. An unspecific protein, like casein, does not reproduce this effect, showing that albumin's effect is specific. Our work describes the first specific inducers of natural competence inA. baumannii. Overall, our results suggest that the main protein in blood enhances HGT inA. baumannii, contributing to the increase of AMR in this threatening human pathogen.

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex

1999 ◽  
Vol 91 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Oliver Ganslandt ◽  
Rudolf Fahlbusch ◽  
Christopher Nimsky ◽  
Helmut Kober ◽  
Martin Möller ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Three Dimensional ◽  
Image Data ◽  
Data Set ◽  
Content Type ◽  
Promising Tool ◽  
Neuronavigation System ◽  
Functional Neuronavigation ◽  
Intraoperative Recording ◽  
Fine Print

Object. The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed.Methods. The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image and the image data set was implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyri were identified by neuronavigation and, in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the procedure.Conclusions. The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to lessen morbidity around eloquent brain areas.

scholarly journals Molecular Analysis of the Acinetobacter baumannii Biofilm-Associated Protein

2013 ◽  
Vol 79 (21) ◽  
pp. 6535-6543 ◽  
Author(s):  
H. M. Sharon Goh ◽  
Scott A. Beatson ◽  
Makrina Totsika ◽  
Danilo G. Moriel ◽  
Minh-Duy Phan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Biofilm Growth ◽  
Content Type ◽  
Amino Acid Region ◽  
Carbapenem Resistant ◽  
C Terminus ◽  
And Function

ABSTRACTAcinetobacter baumanniiis a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability ofA. baumanniito survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of theA. baumanniibiofilm-associated protein (Bap) in 24 carbapenem-resistantA. baumanniiST92 strains isolated from a single institution over a 10-year period. Thebapgene was highly prevalent, with 22/24 strains being positive forbapby PCR. Partial sequencing ofbapwas performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that BapMS1968clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, thebapMS1968gene was cloned, and its expression in a recombinantEscherichia colistrain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority ofA. baumanniistrains expressed an ∼200-kDa Bap protein. Further analysis of three Bap-positiveA. baumanniistrains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth byA. baumanniiclinical isolates.

scholarly journals Molecular docking, dynamics and free energy analyses of Acinetobacter baumannii OXA class enzymes with carbapenems investigating their hydrolytic mechanisms

2020 ◽  
Vol 69 (8) ◽  
pp. 1062-1078
Author(s):  
Balajee Ramachandran ◽  
Jeyaraman Jeyakanthan ◽  
Bruno S. Lopes
Keyword(s):  
Free Energy ◽  
Acinetobacter Baumannii ◽  
Type Species ◽  
Three Dimensional ◽  
World Health ◽  
Phenotypic Data ◽  
Content Type ◽  
Beta Lactamases ◽  
Link Type ◽  
Class D

Introduction. Acinetobacter baumannii is a critical priority pathogen listed by the World Health Organization due to increasing levels of resistance to carbapenem classes of antibiotics. It causes wound and other nosocomial infections, which can be life-threatening. Hence, there is an urgent need for the development of new classes of antibiotics. Aim. To study the interaction of carabapenems with class D beta-lactamases (oxacillinases) and analyse drug resistance by studying enzyme–substrate complexes using modelling approaches as a means of establishing correlations with the phenotypic data. Methodology. The three-dimensional structures of carbapenems (doripenem, ertapenem, imipenem and meropenem) were obtained from DrugBank and screened against class D beta-lactamases. Further, the study was extended with their variants. The variants’ structure was homology-modelled using the Schrödinger Prime module (Schrödinger LLC, NY, USA). Results. The first discovered intrinsic beta-lactamase of Acinetobacter baumannii , OXA-51, had a binding energy value of −40.984 kcal mol−1, whereas other OXA-51 variants, such as OXA-64, OXA-110 and OXA-111, have values of −60.638, –66.756 and −67.751 kcal mol−1, respectively. The free energy values of OXA-51 variants produced better results than those of other groups. Conclusions. Imipenem and meropenem showed MIC values of 2 and 8 µg ml−1, respectively against OXA-51 in earlier studies, indicating that these are the most effective drugs for treatment of A. baumannii infection. According to our results, OXA-51 is an active enzyme that shows better interactions and is capable of hydrolyzing carbapenems. When correlating the hydrogen-bonding interaction with MIC values, the predicted results are in good agreement and might provide initial insights into performing similar studies related to OXA variants or other antibiotic–enzyme-based studies.

scholarly journals The Acinetobacter baumannii Biofilm-Associated Protein Plays a Role in Adherence to Human Epithelial Cells

2011 ◽  
Vol 80 (1) ◽  
pp. 228-233 ◽  
Author(s):  
Kari A. Brossard ◽  
Anthony A. Campagnari
Keyword(s):  
Epithelial Cells ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Bacterial Colonization ◽  
Water Channel ◽  
Cell Surface Hydrophobicity ◽  
Health Care Facilities ◽  
Content Type ◽  
Abiotic Surfaces ◽  
Normal Human

ABSTRACTAcinetobacter baumanniiis a significant source of nosocomial infections worldwide. This bacterium has the ability to survive and persist on multiple abiotic surfaces in health care facilities, and once a focus has been established, this opportunistic pathogen is difficult to eradicate. This paper demonstrates that theA. baumanniibiofilm-associated protein (Bap) is necessary for mature biofilm formation on medically relevant surfaces, including polypropylene, polystyrene, and titanium. Scanning electron microscopy analyses of biofilms show that Bap is required for three-dimensional tower structure and water channel formation. In conjunction with persistence on abiotic surfaces, adherence to eukaryotic cells is an important step in bacterial colonization resulting in infection of the host. We have described Bap as the surface structure involved in adherence ofA. baumanniito both normal human bronchial epithelial cells and normal human neonatal keratinocytes. However, Bap is not involved in internalization of the bacterium in these two cell lines. Furthermore, this study shows that the presence of Bap increases the bacterial cell surface hydrophobicity. The results of this study are pertinent, as the data lead to a better understanding of the role of Bap in biofilm formation on medical surfaces and in colonization of the host.

scholarly journals New Mutations Involved in Colistin Resistance in Acinetobacter baumannii

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Bingbing Sun ◽  
Haiyan Liu ◽  
Yu Jiang ◽  
Lei Shao ◽  
Sheng Yang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
World Health ◽  
Mutant Library ◽  
Colistin Resistance ◽  
Content Type ◽  
Wide Range ◽  
Resistant Mutants

ABSTRACT Colistin is used as the “last resort” to treat infections caused by multidrug-resistant Acinetobacter baumannii, which is at the top of the World Health Organization’s list of the most dangerous bacterial species that threaten human health. Unfortunately, colistin resistance has emerged in A. baumannii. To broaden the study of the resistance mechanism of colistin in A. baumannii, we obtained colistin-resistant mutants via two methods: (i) screening and isolation from a mariner-based A. baumannii ATCC 19606 transposon mutant library; (ii) selection from challenge of ATCC 19606 with successively increasing concentrations of colistin. A total of 41 mutants with colistin MIC of 4 μg/ml to 64 μg/ml were obtained by transposon mutant library screening. Five highly resistant mutants with colistin MICs ranging from 256 μg/ml to 512 μg/ml were selected from successive colistin challenges. Genotypic complementation and remodeling of the transposon mutants revealed that the genes inactivated by the transposon insertion were not responsible for resistance. Whole-genome sequence analysis of the colistin-resistant strains revealed that the main causes of the resistance to colistin were mutations in the pmrA-pmrB genes, including pmrAP102R, pmrBP233S, and pmrBT235N and the novel alleles pmrAI13M and pmrBQ270P. Interestingly, we found that miaAI221V mutation of A. baumannii strain ATCC 19606 (pmrAP102R) resulted in 4-fold increases in the colistin MIC, which rose from 32 μg/ml to 128 μg/ml. But miaAI221V itself had little effect on the colistin susceptibility of ATCC 19606. These data broaden knowledge of the scope of chromosomally encoded mechanisms of resistance to colistin. IMPORTANCE Acinetobacter baumannii is an important Gram-negative opportunistic pathogen commonly infecting critically ill patients. It possesses a remarkable ability to survive in the hospital environment and acquires resistance determinants corresponding to a wide range of antibacterial agents. Given that the current treatment options for multidrug resistant A. baumannii are extremely limited, colistin administration has become the treatment of last resort. However, colistin-resistant A. baumannii strains have recently been reported. The mechanism of resistance to colistin in A. baumannii has rarely been reported. Here, we found two novel mutations in pmrA (I13M) and pmrB (Q270P) that caused colistin resistance. It is also first reported here that the presence of miaA with a I221V mutation enhanced the colistin resistance of pmrAP102R.

scholarly journals Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in Acinetobacter baumannii

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Eun-Jeong Yoon ◽  
Yassine Nait Chabane ◽  
Sylvie Goussard ◽  
Erik Snesrud ◽  
Patrice Courvalin ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Cell Division ◽  
Acinetobacter Baumannii ◽  
Resistance Gene ◽  
Biofilm Formation ◽  
Hospital Environment ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Clinical Resistance ◽  
Isogenic Mutants

ABSTRACTAcinetobacter baumanniiis a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptibleA. baumanniistrain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance.IMPORTANCEIncreased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance.Acinetobacter baumanniihas recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptibleA. baumanniiclinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition.

Effect of Ultrasound Intensity and Mode on Piroxicam Transport Across Three-Dimensional Skin Equivalent Epiderm™

2020 ◽  
Vol 14 (1) ◽  
pp. 75-83
Author(s):  
Mohammed A. Alarjah
Keyword(s):  
Stratum Corneum ◽  
Barrier Function ◽  
Three Dimensional ◽  
Low Frequency ◽  
Ultrasonic Waves ◽  
Skin Equivalent ◽  
Skin Permeability ◽  
Three Dimension ◽  
Chromatography Method ◽  
Ultrasound Waves

Background: Transdermal drug delivery has many advantages compared to other routes. However, the barrier function of the stratum corneum limits the use of the skin as an administrative route for medications. Different methods were investigated to alter the barrier function of the stratum corneum and it was found that applying different ultrasound waves could enhance the skin's permeability. Objective: The aim of this work is to study the effect of ultrasonic waves on the alteration of skin natural barrier function, to improve the permeability of the skin to Piroxicam using three-dimension skin (EpiDermTM) as a skin model for the investigation. Method: The effect of ultrasound at 1 MHz and 20 kHz on the permeation of Piroxicam across the three-dimensional skin equivalent using a Franz diffusion cell, was evaluated and the concentration of Piroxicam in the receiving compartment was determined using liquid chromatography method. Results: The permeation of Piroxicam enhanced by 199% when therapeutic ultrasound at 1 MHz frequency was used. Significant permeation enhancement was also found upon utilizing low frequency sonophoresis at 20 kHz (427%) with no apparent damage to the membrane. Conclusion: Sonophoresis has a positive effect on enhancing skin permeability. The enhancement level was largely dependent on the sonication factors; frequency, intensity and length of treatment. Multiple mechanisms of action might be involved in permeation improvement of the piroxicam molecule. Those mechanisms are largely dependent on the ultrasonic conditions.

scholarly journals To Make or Take: Bacterial Lipid Homeostasis during Infection

mBio ◽  
2021 ◽  
Author(s):  
Felise G. Adams ◽  
Claudia Trappetti ◽  
Jack K. Waters ◽  
Maoge Zang ◽  
Erin B. Brazel ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Morbidity And Mortality ◽  
Hospital Environment ◽  
Lipid Homeostasis ◽  
Significant Morbidity ◽  
Changing Environment ◽  
Content Type ◽  
Bacterial Lipid

Acinetobacter baumannii is one of the world’s most problematic superbugs and is associated with significant morbidity and mortality in the hospital environment. The critical need for new antimicrobial strategies is recognized, but our understanding of its behavior and adaptation to a changing environment during infection is limited.

Adaptations of carbapenem resistant Acinetobacter baumannii (CRAB) in the hospital environment causing sustained outbreak

2021 ◽  
Vol 70 (3) ◽  
Author(s):  
Swati Sharma ◽  
Arghya Das ◽  
Tuhina Banerjee ◽  
Hiranmay Barman ◽  
Ghanshyam Yadav ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Type Species ◽  
Hospital Environment ◽  
Genetic Profile ◽  
Content Type ◽  
Slow Growth Rate ◽  
Link Type ◽  
Carbapenem Resistant

Introduction. Carbapenem resistance in Acinetobacter baumannii ( A. baumannii ) is an emerging global threat. Gap statement. The adaptation strategies of A. baumannii for this emergence as a nosocomial pathogen has been less studied. Aim. This prospective study analysed a sustained outbreak of carbapenem resistant Acinetobacter baumannii (CRAB) in the intensive care unit (ICU) with reference to antimicrobial resistance and virulence in the colonizing and pathogenic isolates under carbapenem stress. Results. The CRAB isolates from initial and sustained outbreak were found harbouring multiple carbapenemase genes. These genes included bla OXA-23 ,bla IMP, bla VIM and bla NDM. From NICU environment three phenotypically carbapenem susceptible isolates were found carrying bla OXA-23, bla IMP, bla VIM genes. Prior imipenem therapy was one of the risk factors (P=0.0016). The outbreak was polyclonal. Under imipenem stress, outbreak isolates showed no loss of carbapenemase genes against stress free conditions (23.7±1.33 days). Biofilm formation increased with imipenem concentration, with outbreak isolates producing highest biomass. While the pathogens showed a slow growth rate on imipenem exposure, the colonisers grew rapidly (P <0.0001). Methods. Sustained outbreak of CRAB was identified in the ICU (July 2015 to December 2017). Risk factors for acquisition of CRAB was studied. A. baumannii isolates were also collected from the environments of ICU and neonatal ICU (NICU) and blood cultures of septic neonates. Isolates were characterized based on antimicrobial susceptibility, genetic profile, integrons carriage and clonality. Biofilm formation and growth kinetics were studied under varying carbapenem stress. Conclusion. Intense carbapenem exposure in the ICU facilitates persistence of CRAB by several adaptations causing sustained outbreaks.

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