Novel Approach Leads to Potential Sepsis Prevention in Burn Patients
Immediately following severe burns, bacteria reach the wound from different sources,
including the patient’s skin, gastrointestinal tract, respiratory tracts and health
care-related human contact. Within the wound, bacteria multiply, establish an infection
and move from the infected burn wound into the bloodstream, causing serious complications
like sepsis, multiple-organ failure and death.
In modern burn units, more than 50% of deaths are attributed to septic shock and organ
dysfunction. Pseudomonas aeruginosa, an opportunistic pathogen, is among the different
pathogens that cause sepsis in burn patients. This gram-negative, antibiotic-resistant
bacterium produces several destructive factors that make it critical to identify alternative
treatments.
To help reduce the risk of Pseudomonas aeruginosa infection and its associated complications,
Abdul Hamood, Ph.D., a professor for the Department of Immunology and Molecular Microbiology
at the Texas Tech University Health Sciences Center (TTUHSC) School of Medicine, and
a team of collaborators investigated the feasibility of developing a topical treatment
unrelated to conventional antibiotics that can be used to battle Pseudomonas aeruginosa.
Their study, “Application of Lactobacillus gasseri 63 AM supernatant to Pseudomonas
aeruginosa-infected wounds prevents sepsis in murine models of thermal injury and
dorsal excision,” is published in the August issue of the Journal of Medical Microbiology.
Because Pseudomonas aeruginosa has developed resistance to antibiotics, Taylor Lenzmeier,
a TTUHSC graduate student and the study’s lead author, said Hamood’s research uses
probiotic bacteria and its superior by-products to prevent Pseudomonas infection.
“It's almost this idea of using probiotics as an alternative to antibiotics,” Lenzmeier
explained. “What makes it really, really special is the bacteria that is creating
this alternative is a very safe bacteria already found in the gut, the mouth and all
over the human body. We're using the safe bacteria to get rid of the pathogenic bacteria.”
To accomplish this, the Hamood team examined the effectiveness of using a highly concentrated
supernatant, or secreted liquid by-product, obtained from Lactobacillus gasseri strain
63 AM (LgCS). This supernatant is separated from the LgCS, concentrated and applied
to the wound. Lenzmeier said other similar research exists, but in those studies the
bacteria is added to the wound prior to secretion.
“It seems kind of counterintuitive to use one bacteria to get rid of another bacterial
infection, so we completely eliminate that process,” Lenzmeier said. “We take this
LgCS bacteria, let it secrete, and then add those secretions instead of adding the
bacteria and letting it secrete within the wound.”
The process also prevents the bacteria from entering the bloodstream where it may
or may not be safe for the patient, she added.
The research team found that applying LgCS secretions to the wound inhibited Pseudomonas
aeruginosa growth, prevented biofilm development and eliminated any partially developed
biofilm. Biofilms are sticky substances that form whenever bacteria attaches to surfaces
in moist conditions like thermal (burn) injuries.
The study also showed that a single injection of LgCS secretions administered after
thermal injury and Pseudomonas aeruginosainfection reduced mortality to 0% and prevented
sepsis in mice. A second injection administered 24 hours later eliminated Pseudomonas
aeruginosafrom the wound.
In addition, and using another model of wound infection that does not involve thermal
injury, the investigators discovered that treating an infected wound using either
LgCS or ceftazidime significantly reduced the mortality rate in mice, and treating
the infected wound using a combination of LgCS and ceftazidime eliminated mortality
in mice. Ceftazidime is an antibiotic used to treat meningitis and several other infections.
Armed with these results, Hamood said the next step is to characterize the inhibitory
factor that seems to produce such promising results. For this study, his team harvested
everything the LgCS secreted and concentrated it by 20 times. Now they must uncover
the nature of the inhibiting factor and learn for certain if it’s a protein or an
enzyme.
“Right now, it's just a crude product, and we proved that this crude product is very
special,” Hamood said. “There's a phenomenon occurring, but now we need to discuss
and describe what's causing it, and even further, describe the mechanism of action
to that wound. That’s where I'm going next.”
In addition to Lenzmeier, Hamood’s collaborators included Gary Ventolini, M.D., TTUHSC
regional dean and professor of obstetrics and gynecology; TTUHSC graduate student
Aatiya Ahmad; TTUHSC Research Associate Nithya S. Mudaliar, M.S.; Lt. Cmdr. Mark P.
Simons, Lt. Chase Watters and Joshua A. Stanbro from the Naval Medical Research Center;John
C. Zak, Ph.D., professor, associate dean and chair for the Department of Biological
Sciences at Texas Tech University; and Jane A. Colmer-Hamood, Ph.D., TTUHSC associate
professor.
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