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.

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.

scholarly journals Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291

mSphere ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Brintha P. Girinathan ◽  
Marc Monot ◽  
Daniel Boyle ◽  
Kathleen N. McAllister ◽  
Joseph A. Sorg ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Toxin Production ◽  
Hospitalized Patients ◽  
Host Tissue ◽  
Hospital Environment ◽  
Pivotal Role ◽  
Toxin Gene ◽  
Bacterial Cells ◽  
Significant Morbidity ◽  
Content Type

ABSTRACT C. difficile infects thousands of hospitalized patients every year, causing significant morbidity and mortality. C. difficile spores play a pivotal role in the transmission of the pathogen in the hospital environment. During infection, the spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. Thus, sporulation and toxin production are two important traits of C. difficile. In this study, we showed that a mutation in tcdR, the toxin gene regulator, affects both toxin production and sporulation in epidemic-type C. difficile strain R20291. Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts normally protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB, are part of a pathogenicity locus, which also includes the tcdR gene that codes for TcdR, an alternate sigma factor that initiates transcription of tcdA and tcdB genes. We created a tcdR mutant in epidemic-type C. difficile strain R20291 in an attempt to identify the global role of tcdR. A site-directed mutation in tcdR affected both toxin production and sporulation in C. difficile R20291. Spores of the tcdR mutant were more heat sensitive than the wild type (WT). Nearly 3-fold more taurocholate was needed to germinate spores from the tcdR mutant than to germinate the spores prepared from the WT strain. Transmission electron microscopic analysis of the spores also revealed a weakly assembled exosporium on the tcdR mutant spores. Accordingly, comparative transcriptome analysis showed many differentially expressed sporulation genes in the tcdR mutant compared to the WT strain. These data suggest that regulatory networks of toxin production and sporulation in C. difficile strain R20291 are linked with each other. IMPORTANCE C. difficile infects thousands of hospitalized patients every year, causing significant morbidity and mortality. C. difficile spores play a pivotal role in the transmission of the pathogen in the hospital environment. During infection, the spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. Thus, sporulation and toxin production are two important traits of C. difficile. In this study, we showed that a mutation in tcdR, the toxin gene regulator, affects both toxin production and sporulation in epidemic-type C. difficile strain R20291.

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 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 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 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.

scholarly journals Characterization of Carbapenem-Resistant Acinetobacter baumannii Isolates from Clinical Specimens

2021 ◽  
Vol 10 (29) ◽  
Author(s):  
Khansaa Abdullah ◽  
Peter C. Iwen ◽  
Baha Abdalhamid
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Draft Genome ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Genome Sequences ◽  
Content Type ◽  
Clinical Specimens ◽  
Carbapenem Resistant

Carbapenem-resistant Acinetobacter baumannii is an urgent threat worldwide. This bacterium is associated with high morbidity and mortality, with limited available treatment options. Here, we report the draft genome sequences of five carbapenem-resistant Acinetobacter baumannii isolates from human samples.

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.

scholarly journals Discrimination of hospital isolates of Acinetobacter baumannii using repeated sequences and whole genome alignment differential analysis

2021 ◽  
Author(s):  
Roman Kotłowski ◽  
Alicja Nowak-Zaleska ◽  
Grzegorz Węgrzyn
Keyword(s):  
Acinetobacter Baumannii ◽  
Time Frame ◽  
Repeated Sequences ◽  
Hospital Environment ◽  
Genome Alignment ◽  
Whole Genome ◽  
Differential Analysis ◽  
Gene Encoding ◽  
Resistance Patterns ◽  
Whole Genome Alignment

AbstractAn optimized method for bacterial strain differentiation, based on combination of Repeated Sequences and Whole Genome Alignment Differential Analysis (RS&WGADA), is presented in this report. In this analysis, 51 Acinetobacter baumannii multidrug-resistance strains from one hospital environment and patients from 14 hospital wards were classified on the basis of polymorphisms of repeated sequences located in CRISPR region, variation in the gene encoding the EmrA-homologue of E. coli, and antibiotic resistance patterns, in combination with three newly identified polymorphic regions in the genomes of A. baumannii clinical isolates. Differential analysis of two similarity matrices between different genotypes and resistance patterns allowed to distinguish three significant correlations (p < 0.05) between 172 bp DNA insertion combined with resistance to chloramphenicol and gentamycin. Interestingly, 45 and 55 bp DNA insertions within the CRISPR region were identified, and combined during analyses with resistance/susceptibility to trimethoprim/sulfamethoxazole. Moreover, 184 or 1374 bp DNA length polymorphisms in the genomic region located upstream of the GTP cyclohydrolase I gene, associated mainly with imipenem susceptibility, was identified. In addition, considerable nucleotide polymorphism of the gene encoding the gamma/tau subunit of DNA polymerase III, an enzyme crucial for bacterial DNA replication, was discovered. The differentiation analysis performed using the above described approach allowed us to monitor the distribution of A. baumannii isolates in different wards of the hospital in the time frame of several years, indicating that the optimized method may be useful in hospital epidemiological studies, particularly in identification of the source of primary infections.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

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