Skin and Soft Tissue Models for Acinetobacter baumannii Infection

Zurawski, Daniel V.; Banerjee, Jaideep; Alamneh, Yonas; Shearer, Jonathan P.; Demons, Samandra

doi:10.1007/978-1-4939-9118-1_25

Cited by 17 publications

(17 citation statements)

References 39 publications

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“…A. baumannii is a successful pathogen which often causes infections of humans and aquatic animals [ 14 ]. It usually causes bacteremia, pneumonia, meningitis, peritonitis, endocarditis, and urinary tract and skin infections [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis of Drug-Resistance Acinetobacter baumannii under the Stress Condition Caused by Litsea cubeba L. Essential Oil via RNA Sequencing

Yang

Hao

Jiang

et al. 2021

Genes

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Litsea cubeba L. essential oil (LCEO) can affect the growth of drug-resistance bacteria. However, research on stress response of drug-resistant A. baumannii under sub-lethal LCEO concentrations had been limited so far. Therefore, transcriptomic analysis of A. baumannii under 1/2 minimum inhibitory concentration (MIC, 0.54 mg/mL) of LCEO was performed. Results of transcriptomic analysis showed that 320/352 genes were significantly up/down-regulated, respectively, in LCEO-treated A. baumannii. Both up and down-regulated genes were significantly enriched in three GO terms (oxidation-reduction process; oxidoreductase activity; oxidoreductase activity, acting on the CH-CH group of donors), which indicated that the redox state of A. baumannii was significantly affected by LCEO. LCEO may also inhibit aerobic respiration, synthesis of ketone bodies and the metabolism of some amino acids while, meanwhile, promoting fatty acid degradation of A. baumannii according to Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The permeability and the stress of cell membrane of A. baumannii were significantly affected by LCEO. After crystal violet dyeing, the biofilm formation of A. baumannii was promoted/inhibited by extremely low/relatively high concentration of LCEO, respectively. LCEO and chloramphenicol have synergistic growth inhibitory effect against A. baumannii according to the Fractional Inhibitory Concentration Index (FICI) value = 0.375. Our results indicate that the growth of A. baumannii was inhibited by LCEO, and give insights into the stress response of A. baumannii under sub-lethal concentrations of LCEO. These results provided evidence that A. baumannii was inhibited by LCEO, and expanded knowledges of stress response of A. baumannii under sub-lethal concentration of LCEO.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis of Drug-Resistance Acinetobacter baumannii under the Stress Condition Caused by Litsea cubeba L. Essential Oil via RNA Sequencing

Yang

Hao

Jiang

et al. 2021

Genes

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“…A. baumannii is a Gram-negative bacterium that is ubiquitous in nature and a commensal of human skin, present in 20–25% of humans [ 73 ]. The bacterium can be pathogenic as it adheres to and invades human host cells causing bacteraemia, wound infections, pneumonia, endocarditis or meningitis [ 74 , 75 , 76 , 77 , 78 , 79 ]. A. baumannii has been identified as an important nosocomial pathogen due to its ability to form biofilms, modulate host cell signalling, induce apoptosis, develop serum resistance, and perform immune evasion [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

First Description of the Composition and the Functional Capabilities of the Skin Microbial Community Accompanying Severe Scabies Infestation in Humans

et al. 2021

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Epidemiological studies link Sarcoptes scabiei infection and impetigo. Scabies mites can promote Streptococcus pyogenes (Group A Streptococcus) and Staphylococcus aureus infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. However, little is known about the composition and the function of the scabies-associated microbiota. Here, high-throughput whole-metagenome sequencing was used to explore the scabies-associated microbiome. Scabies mites including their immediate microenvironments were isolated from two patients with severe scabies in Northern Australia. Two ~45–50 million paired-end reads Illumina libraries were generated of which ~2 (5.1%) and 0.7 million (1.3%) microbial reads were filtered out by mapping to human (hg19) and mite draft genomes. Taxonomic profiling revealed a microbial community dominated by the phylum Firmicutes (A: 79% and B: 59%) and genera that comprise Streptococcus, Staphylococcus, Acinetobacter, and Corynebacterium. Assembly of the metagenome reads resulted in genome bins representing reference genomes of Acinetobacter baumannii, Streptococcus dysgalactiae (Group C/G), Proteus mirablis and Staphylococcus aureus. The contigs contained genes relevant to pathogenicity and antibiotics resistance. Confocal microscopy of a patient skin sample confirmed A. baumannii, Streptococci and S. aureus in scabies mite gut and faeces and the surrounding skin. The study provides fundamental evidence for the association of opportunistic pathogens with scabies infection.

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“…Mice are shaved and cleaned prior to performing the wounding procedure, the area on the dorsum was cleaned with alcohol and iodine. Then, a 6 mm punch biopsy was performed resulting in a full thickness wound, which was followed by pipetting 25 µL of bacterial culture inoculum onto the wound site, corresponding to 5.0 × 10 4 CFU of a bioluminescent variant of AB5075::lux that was previously developed and described 29,30,37 . This inoculum was administered directly onto the center of the wound and allowed to incubate for ~10 min before a Tegaderm™ dressing was applied over the wound.…”

Section: Murine Wound Model Of Infectionmentioning

confidence: 99%

The polymyxin SPR206 remediates gram-negative infections in vivo

Fitzgerald,

Castellanos,

Escatte

et al. 2023

Preprint

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ESKAPEE pathogens (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), particularly the gram-negative species, are a problematic group of bacteria associated with nosocomial infections in susceptible patients. These infections are often further complicated by multidrug-resistant (MDR) strains and a lack of treatment options. While the pipeline of new antibiotics is nothing short of thin when it comes to gram-negative activity, one promising molecule is SPR206. SPR206 is a novel polymyxin antibiotic, a nonapeptide designed to overcome the nephrotoxicity associated with other members of this drug class. As intended, SPR206 was found to be safe with no severe adverse events in a Phase 1, single ascending dose/multiple ascending dose clinical trial. SPR206 has in vitro activity against almost all gram-negative species, and we confirmed this activity in minimal inhibitory concentration assays against unique diversity sets of bacterial isolates. Additionally, bactericidal activity was observed in time-kill assays, which is expected for polymyxins. Subsequently, we evaluated the safety and efficacy of SPR206 in three separate in vivo models: Galleria mellonella and two murine models, a pulmonary model and a wound model. In G. mellonella and in the mouse pulmonary model, SPR206 provided almost 100% survival in treated animal groups when compared to untreated control groups. With wound infection, SPR206 significantly reduced bacterial burden and decreased time to heal compared to untreated groups. With wound infection, SPR206 significantly reduced bacterial burden and decreased time to heal compared to untreated groups. These results suggest SPR206 is a potent antibiotic with MDR gram-negative activity that could have expanded clinical indications to include skin and soft tissue infection and hospital-acquired pneumonia.

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Skin and Soft Tissue Models for Acinetobacter baumannii Infection

Cited by 17 publications

References 39 publications

Transcriptomic Analysis of Drug-Resistance Acinetobacter baumannii under the Stress Condition Caused by Litsea cubeba L. Essential Oil via RNA Sequencing

Transcriptomic Analysis of Drug-Resistance Acinetobacter baumannii under the Stress Condition Caused by Litsea cubeba L. Essential Oil via RNA Sequencing

First Description of the Composition and the Functional Capabilities of the Skin Microbial Community Accompanying Severe Scabies Infestation in Humans

The polymyxin SPR206 remediates gram-negative infections in vivo

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