Genome Sequence of a Virulent
            <i>Pseudomonas aeruginosa</i>
            Strain, 12-4-4(59), Isolated from the Blood Culture of a Burn Patient

Karna, S. L. Rajasekhar; Chen, Tsute; Chen, Ping; Peacock, Trent J; Abercrombie, Johnathan J.; Leung, Kai P.

doi:10.1128/genomea.00079-16

Cited by 11 publications

(9 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This strain was isolated at the Brooke Army Medical Center (Joint Base San Antonio [JBSA]-Fort Sam Houston, TX) from a female burn patient with partial- and full-thickness burns comprising 70% TBSA. 38,49 P. aeruginosa formed robust wound infections regardless of inoculation level. In the wound tissue, several biofilm-associated genes were significantly upregulated.…”

mentioning

confidence: 96%

Development ofPseudomonas aeruginosaBiofilms in Partial-Thickness Burn Wounds Using a Sprague-Dawley Rat Model

Brandenburg

Weaver

Qian

et al. 2018

Journal of Burn Care &Amp; Research

Self Cite

View full text Add to dashboard Cite

We used a modified Walker-Mason scald burn rat model to demonstrate that Pseudomonas aeruginosa, a common opportunistic pathogen in the burn ward and notable biofilm former, establishes biofilms within deep partial-thickness burn wounds in rats.Deep partial-thickness burn wounds, ~10% of the TBSA, were created in anesthetized male Sprague-Dawley rats (350-450 g; n = 84). Immediately post-burn, 100 µl of P. aeruginosa in phosphate-buffered saline at 1 × 103, 1 × 104, or 1 × 105 cells/wound was spread over the burn surface . At 1, 3, 7, and 11 days post-burn, animals were euthanized and blood and tissue were collected for complete blood counts, colony-forming unit (CFU) counts, biofilm gene expression, histology, scanning electron microscopy (SEM), and myeloperoxidase activity in the burn eschar.P. aeruginosa developed robust biofilm wound infections, plateauing at ~1 × 109 CFU/g burn tissue within 7 days regardless of inoculum size. Expression of Pseudomonas alginate genes and other virulence factors in the infected wound indicated formation of mature P. aeruginosa biofilm within the burn eschar. Compared to un-inoculated wounds, P. aeruginosa infection caused both local and systemic immune responses demonstrated by changes in systemic neutrophil counts, histology, and myeloperoxidase activity within the burn wound. Additionally, SEM showed P. aeruginosa enmeshed within an extracellular matrix on the burn surface as well as penetrating 500-600 µm deep into the eschar.P. aeruginosa establishes biofilms within deep partial-thickness burn wounds and invades deep into the burned tissue. This new in vivo biofilm infection model is valuable for testing novel anti-biofilm agents to advance burn care.

show abstract

mentioning

confidence: 96%

Development ofPseudomonas aeruginosaBiofilms in Partial-Thickness Burn Wounds Using a Sprague-Dawley Rat Model

Brandenburg

Weaver

Qian

et al. 2018

Journal of Burn Care &Amp; Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…7). Whole genome sequences of 58 isolates were compared to references from GenBank revealing highest similarities with strain RIVM-EMC2982, a clinical isolate from the Netherlands (CP016955.1), 12-4-4(59), a strain isolated from blood of a burn patient (NZ_CP013696.1 48 ) and W36662, a strain isolated from a cancer patient (CP008870.2). All strains from patient 1 belong to a single clonal clade (W36662), while sequences of isolates of patient 2 indicated a recent and ongoing superinfection by different clones (RIVM-EMC2982 and more recently 12-4-4(59)).…”

Section: Resultsmentioning

confidence: 99%

Evolution of Antibiotic Tolerance Shapes Resistance Development in ChronicPseudomonas aeruginosaInfections

Santi

Manfredi²,

Maffei³

et al. 2020

Preprint

View full text Add to dashboard Cite

The widespread use of antibiotics promotes the evolution and dissemination of resistance and tolerance mechanisms. To assess the relevance of tolerance and its implications for resistance development, we used in vitro evolution and analyzed in-patient microevolution of Pseudomonas aeruginosa, an important human pathogen causing acute and chronic infections. We show that the development of tolerance precedes and promotes the acquisition of resistance in vitro and we present evidence that similar processes shape antibiotic exposure in human patients. Our data suggest that during chronic infections, P. aeruginosa first acquires moderate drug tolerance before following distinct evolutionary trajectories that lead to high-level multi-drug tolerance or to antibiotic resistance. Our studies propose that the development of antibiotic tolerance predisposes bacteria for the acquisition of resistance at early stages of infection and that both mechanisms independently promote bacterial survival during antibiotic treatment at later stages of chronic infections.

show abstract

“…Similar neutrophil and cytokine reactions have been noted to occur in other studies during acute P. aeruginosa infections, resulting in greater tissue damage, inflammation, and no clearance of the pathogen (Rumbaugh et al, 2001;Steinstraesser et al, 2005;Ding et al, 2015;Lin and Kazmierczak, 2017). While typical burn wounds struggle to heal due to poor orchestration of cellular and cytokine responses, the presence of P. aeruginosa appears to worsen the healing by inducing greater neutrophil influx, while also delaying clearance of necrotic neutrophils, which is further hampered by biofilm formation during later stages of infection (Diaz et al, 2008;Sun et al, 2012;Alhede et al, 2014;Karna et al, 2016). This continuing damage with no resolution may ultimately result in a chronic infection by P. aeruginosa (Bjarnsholt et al, 2008;Kirketerp-Moller et al, 2008;Fazli et al, 2009;Lin and Kazmierczak, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…On the day of the burn, rats were anesthetized with isoflurane, placed into the mold and administered a DPT or FT burn equating to 10% total body surface area (TBSA), based on Meeh's formula (Gilpin, 1996). Immediately following the burn, the wound surface was inoculated with 100 µL of 10 3 or 10 4 CFU/wound of P. aeruginosa (strain 12-4-4) suspended in phosphate buffered saline (PBS) (Karna et al, 2016). Control animals received the same burn injury, but received 100 µL of sterile PBS (i.e., no P. aeruginosa).…”

Section: Overview Of Scald Burn Modelmentioning

confidence: 99%

“…In our previous work, we introduced a modified Walker-Mason scald model for inducing deep-partial thickness (DPT) and full-thickness (FT) burn wounds, followed by infection with a clinical isolate of P. aeruginosa (strain 12-4-4) (Walker et al, 1964;Karna et al, 2016;Brandenburg et al, 2019a,b). This rat model provides consistent burn depths and generates a P. aeruginosa biofilm infection that could be monitored over an 11-days period.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Analysis of the Host Response in a Rat Model of Deep-Partial and Full-Thickness Burn Wounds With Pseudomonas aeruginosa Infection

Weaver

Brandenburg

Smith

et al. 2020

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Burn wound injury affects soldiers and civilians alike, often resulting in a dynamic, but un-orchestrated, host response that can lead to infection, scarring, and potentially death. To mitigate these factors, it is important to have a clinically relevant model of burn wound infection that can be utilized for advancing burn wound treatments. Our previous reports have demonstrated the ability of Pseudomonas aeruginosa to generate a biofilm infection within a modified Walker-Mason rat burn model of deep-partial (DPT) and full-thickness (FT) burn wounds (10% total body surface area) in male Sprague-Dawley rats (350-450 g). Here, we further define this model with respect to the host response when challenged with P. aeruginosa infection between the two burn types. Following burn injury and immediate surface exposure to P. aeruginosa, inflammation at the local and systemic levels were monitored for an 11 days period. Compared to burn-only groups, infection with P. aeruginosa further promoted local inflammation in both DPT and FT burn wounds, which was evident by enhanced cellular influx (including neutrophils and monocytes), increased levels of several pro-inflammatory cytokines (IL-1β, IL-6, GRO/KC, andMIP-1α), and reduced IL-10. Systemically, only minor changes were seen in circulating white blood cells and cytokines; however, increases in high mobility group box-1 (HMGB-1) and hyaluronan, as well as decreases in fibronectin were noted particularly in FT burns. Compared to the burn-only group, P. aeruginosa infection resulted in sustained and/or higher levels of HMGB-1 and hyaluronan. Combined with our previous work that defined the burn depth and development of P. aeruginosa biofilms within the wound, this study further establishes this model by defining the host response to the burn and biofilm-infection. Furthermore, this characterization shows several similarities to what is clinically seen and establishes this model for future use in the development and testing of novel therapeutics for burn wound treatment at home and on the battlefield.

show abstract

Genome Sequence of a Virulent Pseudomonas aeruginosa Strain, 12-4-4(59), Isolated from the Blood Culture of a Burn Patient

Cited by 11 publications

References 9 publications

Development ofPseudomonas aeruginosaBiofilms in Partial-Thickness Burn Wounds Using a Sprague-Dawley Rat Model

Development ofPseudomonas aeruginosaBiofilms in Partial-Thickness Burn Wounds Using a Sprague-Dawley Rat Model

Evolution of Antibiotic Tolerance Shapes Resistance Development in ChronicPseudomonas aeruginosaInfections

Comparative Analysis of the Host Response in a Rat Model of Deep-Partial and Full-Thickness Burn Wounds With Pseudomonas aeruginosa Infection

Contact Info

Product

Resources

About