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

ABSTRACT: In 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.

SUBMITTER: Martinez J

PROVIDER: S-EPMC7910304 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Martinez Jasmine J Razo-Gutierrez Chelsea C Le Casin C Courville Robert R Pimentel Camila C Liu Christine C Fung Sammie E SE Tuttobene Marisel R MR Phan Kimberly K Vila Alejandro J AJ Shahrestani Parvin P Jimenez Veronica V Tolmasky Marcelo E ME Becka Scott A SA Papp-Wallace Krisztina M KM Bonomo Robert A RA Soler-Bistue Alfonso A Sieira Rodrigo R Ramirez Maria Soledad MS

Scientific reports 20210226 1

In 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 ...[more]

PMID: 33637791

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Project description:BackgroundIntracranial infection by Acinetobacter baumannii (A. baumannii) after neurosurgery has always been a difficult problem for neurosurgeons. This study analyzed risk factors that discriminated A. baumannii from other bacteria causing intracranial infection after neurosurgery. It also examined the differences in the cerebrospinal fluid (CSF) indexes to explore their value in the early diagnosis of intracranial infection by A. baumannii.MethodsWe retrospectively reviewed ten years (January 2011 to May 2021) of postoperative central nervous system (CNS) infections in the First Hospital of China Medical University. According to the pathogen, CNS infections were divided into A. baumannii group and other species of bacteria group. We collected clinical and laboratory information of patients, and statistical analysis was performed with SPSS 26.0. Risk factors were screened by univariate analysis, and independent risk factors were screened by multiple logistic regression analysis. Finally, CSF-Pro, CSF-Glu, CSF-Cl, CSF-monocytes (%), CSF-multinucleated cells (%) levels, and CSF multinucleated cells%/monocytes% in the different groups were analyzed.ResultsA total of 155 patients were included, 62 cases (40%) of intracranial infection by A. baumannii and 93 cases (60%) by other species of bacteria. The analysis showed that indwelling nasogastric tubes (P＜0.001, OR = 4.231), indwelling peripherally inserted central catheters (PICCs) (P = 0.041, OR = 2.765), and CSF drainage obstruction (P = 0.003, OR = 3.765) were independent risk factors for intracranial infection by A. baumannii after neurosurgery. Indwelling ventriculoperitoneal shunt (VPS) was a protective factor (P = 0.033, OR = 0.22). In addition, compared with other bacterial groups, the A. baumannii group had higher CSF-pro and CSF- multinucleated cells (%) levels and lower CSF-Glu and CSF- monocytes (%) levels, and the difference was statistically significant (P < 0.01).ConclusionsOur results elucidate risk factors and differences in CSF indexes for intracranial infection by A. baumannii after neurosurgery that could be detected and prevented early to reduce mortality.

Project description:BackgroundInterestingly, Acinetobacter baumannii presents an enhanced capacity to form biofilms (also named pellicles) at the air-liquid interface as compared to the other Acinetobacter species. This characteristic questions the contribution of this phenotype to an increased risk of clinical infections by this pathogen.Methodology/principal findingsBy a proteomic approach using 2-D gel electrophoresis-LC-MS/MS mass spectrometry, we compared the membrane protein patterns of A. baumannii 77, a pellicle-forming clinical isolate, grown in planktonic and in sessile modes. We identified 52 proteins with a differential expression, including 32 up-regulated and 20 down-regulated in the pellicle state. Several proteins, differentially expressed during pellicle development, were of particular interest. We determined the over-expression of four siderophore iron uptake systems including the acinetobactin and enterobactin receptors and confirmed that the development of this type of biofilm is promoted by ferric ions. Two over-expressed proteins, CarO and an OprD-homologue, putative carbapenem-resistance associated porins, would be involved in the transport of specific compounds, like ornithine, a biosynthesis precursor of a siderophore from the hydroxamate family. We evidenced the overexpression of a lipase and a transporter of LCFA that may be involved in the recycling of lipids inside the pellicle matrix. Finally, we demonstrated both by proteomic and by AFM studies that this particular type of biofilm required multiple pili systems to maintain this cohesive structure at the air-liquid interface; two of these systems have never been described in A. baumannii.Conclusions/significanceOur study demonstrated that several proteins, overexpressed at a late state of pellicle development, could be potentially involved in virulence processes. Therefore, regarding the number of potential virulence factors that are over-expressed in this growth mode, the pellicle-forming clinical isolates should be kept under survey.

Project description:The increasing prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) caused nosocomial infections generate significant comorbidity and can cause death among patients. Current treatment options are limited. These infections pose great difficulties for infection control and clinical treatment. To identify the antimicrobial resistance, carbapenemases and genetic relatedness of Acinetobacter baumannii isolates from cerebrospinal fluid (CSF) and blood, a total of 50 nonrepetitive CSF isolates and 44 blood isolates were collected. The resistance phenotypes were determined, and polymerase chain reaction (PCR) was performed to examine the mechanisms of carbapenem resistance. Finally, multilocus sequence typing (MLST) was conducted to determine the genetic relatedness of these isolates. It was observed that 88 of the 94 collected isolates were resistant to imipenem or meropenem. Among them, the blaOXA-23 gene was the most prevalent carbapenemase gene, with an observed detection rate of 91.5% (86/94), followed by the blaOXA-24 gene with a 2.1% detection rate (2/94). Among all carbapenem-resistant Acinetobacter baumannii (CRAB) observations, isolates with the blaOXA-23 gene were resistant to both imipenem and meropenem. Interestingly, isolates positive for the blaOXA-24 gene but negative for the blaOXA-23 gene showed an imipenem-sensitive but meropenem-resistant phenotype. The MLST analysis identified 21 different sequence types (STs), with ST195, ST540 and ST208 most frequently detected (25.5%, 12.8% and 11.7%, respectively). 80 of the 94 isolates (85.1%) were clustered into CC92 which showed a carbapenem resistance phenotype (except AB13). Five novel STs were detected, and most of them belong to CRAB. In conclusion, these findings provide additional observations and epidemiological data of CSF and blood A. baumannii strains, which may improve future infection-control measures and aid in potential clinical treatments in hospitals and other clinical settings.

Project description:BACKGROUND: Acinetobacter baumannii is a significant hospital pathogen, particularly due to the dissemination of highly multidrug resistant isolates. Genome data have revealed that A. baumannii is highly genetically diverse, which correlates with major variations seen at the phenotypic level. Thus far, comparative genomic studies have been aimed at identifying resistance determinants in A. baumannii. In this study, we extend and expand on these analyses to gain greater insight into the virulence factors across eight A. baumannii strains which are clonally, temporally and geographically distinct, and includes an isolate considered non-pathogenic and a community-acquired A. baumannii. RESULTS: We have identified a large number of genes in the A. baumannii genomes that are known to play a role in virulence in other pathogens, such as the recently studied proline-alanine-alanine-arginine (PAAR)-repeat domains of the type VI secretion systems. Not surprising, many virulence candidates appear to be part of the A. baumannii core genome of virulent isolates but were often found to be insertionally disrupted in the avirulent A. baumannii strain SDF. Our study also reveals that many known or putative virulence determinants are restricted to specific clonal lineages, which suggests that these virulence determinants may be crucial for the success of these widespread common clones. It has previously been suggested that the high level of intrinsic and adaptive resistance has enabled the widespread presence of A. baumannii in the hospital environment. This appears to have facilitated the expansion of its repertoire of virulence traits, as in general, the nosocomial strains in this study possess more virulence genes compared to the community-acquired isolate. CONCLUSIONS: Major genetic variation in known or putative virulence factors was seen across the eight strains included in this study, suggesting that virulence mechanisms are complex and multifaceted in A. baumannii. Overall, these analyses increase our understanding of A. baumannii pathogenicity and will assist in future studies determining the significance of virulence factors within clonal lineages and/or across the species.

Dataset Information

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

Publications

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

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