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1.
Viruses ; 16(7)2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-39066163

RÉSUMÉ

The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge.


Sujet(s)
Antibactériens , Carbapénèmes , Multirésistance bactérienne aux médicaments , Phagothérapie , Infections à Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/virologie , Pseudomonas aeruginosa/effets des médicaments et des substances chimiques , Carbapénèmes/pharmacologie , Antibactériens/pharmacologie , Infections à Pseudomonas/thérapie , Infections à Pseudomonas/microbiologie , Biofilms/effets des médicaments et des substances chimiques , Bactériophages/physiologie , Tests de sensibilité microbienne , Humains , Phages de Pseudomonas/physiologie , Imipénem/pharmacologie
2.
Mil Med ; 189(7-8): e1488-e1496, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38780999

RÉSUMÉ

INTRODUCTION: Antibacterial resistance is an emerging problem in military medicine. Disruptions to the health care systems in war-torn countries that result from ongoing conflict can potentially exacerbate this problem and increase the risk to U.S. forces in the deployed environment. Therefore, novel therapies are needed to mitigate the impact of these potentially devastating infections on military operations. Bacteriophages are viruses that infect and kill bacteria. They can be delivered as therapeutic agents and offer a promising alternative to traditional antibiotic chemotherapy. There are several potential benefits to their use, including high specificity and comparative ease of use in the field setting. However, the process of engineering phages for military medical applications can be a laborious and time-consuming endeavor. This review examines available techniques and compares their efficacy. MATERIALS AND METHODS: This review evaluates the scientific literature on the development and application of four methods of bacteriophage genome engineering and their consideration in the context of military applications. Preffered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for a systematic review of available literature that met criteria for analysis and inclusion. The research completed for this review article originated from the United States Military Academy's library "Scout" search engine, which compiles results from 254 available databases (including PubMed, Google Scholar, and SciFinder). Particular attention was focused on identifying useful mechanistic insight into the nature of the engineering technique, the ease of use, and the applicability of the technique to countering the problem of antimicrobial resistance in the military setting. RESULTS: A total of 52 studies were identified that met inclusion criteria following PRISMA guidelines. The bioengineering techniques analyzed included homologous recombination (12 articles), in vivo recombineering (9 articles), bacteriophage recombineering of electroporated DNA (7 articles), and the CRISPR-Cas system (10 articles). Rates of success and fidelity varied across each platform, and comparative benefits and drawbacks are considered. CONCLUSIONS: Each of the phage engineering techniques addressed herein varies in amount of effort and overall success rate. CRISPR-Cas-facilitated modification of phage genomes presents a highly efficient method that does not require a lengthy purification and screening process. It therefore appears to be the method best suited for military medical applications.


Sujet(s)
Bactériophages , Génie génétique , Bactériophages/génétique , Humains , Génie génétique/méthodes , Spécificité d'hôte , Phagothérapie/méthodes
3.
Mil Med ; 2023 Oct 17.
Article de Anglais | MEDLINE | ID: mdl-37847552

RÉSUMÉ

INTRODUCTION: Antibiotic-resistant bacteria are a growing threat to civilian and military health today. Although infections were once easily treatable by antibiotics and wound cleaning, the frequent mutation of bacteria has created strains impermeable to antibiotics and physical attack. Bacteria further their pathogenicity because of their ability to form biofilms on wounds, medical devices, and implant surfaces. Methods for treating biofilms in clinical settings are limited, and when formed by antibiotic-resistant bacteria, can generate chronic infections that are recalcitrant to available therapies. Bacteriophages are natural viral predators of bacteria, and their ability to rapidly destroy their host has led to increased attention in potential phage therapy applications. MATERIALS AND METHODS: The present article sought to address a knowledge gap in the available literature pertaining to the usage of bacteriophage in clinically relevant settings and the resolution of infections particular to military concerns. PRISMA guidelines were followed for a systematic review of available literature that met the criteria for analysis and inclusion. The research completed for this review article originated from the U.S. Military Academy's library "Scout" search engine, which complies results from 254 available databases (including PubMed, Google Scholar, and SciFinder). The search criteria included original studies that employed bacteriophage use against biofilms, as well as successful phage therapy strategies for combating chronic bacterial infections. We specifically explored the use of bacteriophage against antibiotic- and treatment-resistant bacteria. RESULTS: A total of 80 studies were identified that met the inclusion criteria following PRISMA guidelines. The application of bacteriophage has been demonstrated to robustly disrupt biofilm growth in wounds and on implant surfaces. When traditional therapies have failed to disrupt biofilms and chronic infections, a combination of these treatments with phage has proven to be effective, often leading to complete wound healing without reinfection. CONCLUSIONS: This review article examines the available literature where bacteriophages have been utilized to treat biofilms in clinically relevant settings. Specific attention is paid to biofilms on implant medical devices, biofilms formed on wounds, and clinical outcomes, where phage treatment has been efficacious. In addition to the clinical benefit of phage therapies, the military relevance and treatment of combat-related infections is also examined. Phages offer the ability to expand available treatment options in austere environments with relatively low cost and effort, allowing the impacted warfighter to return to duty quicker and healthier.

4.
J Spec Oper Med ; 23(3): 63-69, 2023 Oct 05.
Article de Anglais | MEDLINE | ID: mdl-37253155

RÉSUMÉ

Massive hemorrhaging remains the most common cause of preventable battlefield deaths. Blood used for trauma care requires a robust donation network, capacity for long-term storage, and extensive and accurate testing. Bioengineering technologies could offer a remedy to these constraints in the form of blood substitutes-fluids that could be transfused into patients to provide oxygen, carry away waste, and aid in coagulation-that would be used in prolonged casualty care and in far-forward settings, overcoming the obstacles of distance and time. The different molecular properties of red blood cells (RBCs), blood substitutes, and platelet replacements contribute to their respective utilities, and each type is currently represented in ongoing clinical trials. Hemoglobin oxygen carriers (HBOCs) are the most advanced RBC replacements, many of which are currently being evaluated in clinical trials in the United States and other countries. Despite recent advancements, challenges remaining in the development of blood alternatives include stability, oxygen capacity, and compatibility. The continued research and investment in new technologies has the potential to significantly benefit the treatment of life-threatening emergency injuries, both on the battlefield and in the civilian sector. In this review, we discuss military blood-management practices and military-specific uses of individual blood components, as well as describe and analyze several artificial blood products that could be options for future battlefield use.


Sujet(s)
Substituts sanguins , Médecine militaire , Humains , États-Unis , Substituts sanguins/usage thérapeutique , Hémorragie/prévention et contrôle , Hémoglobines , Oxygène
5.
Med J (Ft Sam Houst Tex) ; (Per 22-01/02/03): 50-55, 2022.
Article de Anglais | MEDLINE | ID: mdl-34940968

RÉSUMÉ

OBJECTIVE: We document a military patient presenting with a diffuse set of symptoms suggestive of chronic Lyme disease (CLD) and the subsequent empiric treatment and health complications arising therein. The lay medical community, spurred by the internet, has ascribed these diffuse symptoms to various illnesses including CLD without confirmatory serological evidence of any underlying disease. With a growing community of patient advocates, CLD has become an illness with broad and highly generalized list of clinical symptoms and an absence of agreed-upon confirmatory laboratory tests. Further complicating matters, diagnostic criteria and treatment protocols differ between the Infectious Diseases Society of America and the International Lyme and Associated Diseases Society guidelines. Clinicians also face serious challenges in diagnosing and treating patients who present with generalized symptoms and close to 50 diagnostic tests for Lyme disease available in North America. Further complicating the picture for military patients seeking medical confirmation of a disease and resolution of their symptoms, medical fitness boards use putative diagnoses as prima faciae evidence in disability. Here a military patient with a long list of complaints that defy any clear or easy diagnosis and treatment is discussed. However, these symptoms taken together with selectively summed notes in the medical record in the absence of convincing and clear laboratory confirmation are suggestive of CLD and its complications, but no resolution was ultimately reached. With the presumptive determination of a medical disability due to CLD by the medical board, the medical dismissal of this service member from active duty occurred.


Sujet(s)
Maladie de Lyme , Personnel militaire , Syndrome post-Lyme , Humains , Maladie de Lyme/diagnostic , Maladie de Lyme/traitement médicamenteux , Amérique du Nord
6.
J Spec Oper Med ; 21(2): 85-88, 2021.
Article de Anglais | MEDLINE | ID: mdl-34105128

RÉSUMÉ

BACKGROUND: Female Servicemembers are increasingly being incorporated into the combat arms and Special Operations communities. Female urinary diversion devices (FUDDs) have been used to facilitate urination in the austere environments that are encountered by Servicemembers. Importantly, the potential for the bacterial contamination of these devices has not been evaluated. The goals of this study were to determine whether microorganisms adhere to the surfaces of FUDDs in the field environment and to demonstrate the presence of potential pathogens on the used devices. MATERIALS AND METHODS: A total of 15 devices that were used in a comprehensive 18-24-hour military field exercise were tested for the presence of microorganisms. Briefly, each device was swabbed, and the swabs were used to inoculate blood agar plates to encourage bacterial growth. The resulting bacterial colonies were identified, and the surface topography of the devices was investigated with electron microscopy. RESULTS: Although microscopy revealed few surface features capable of facilitating bacterial attachment, several species were recovered. Significantly, a biofilm-forming strain of Proteus mirabilis (P. mirabilis) was detected on two of the devices. P. mirabilis is a mobile urinary pathogen that can potentially migrate from the surface of the device into the urinary tract of the user. CONCLUSION: Commercial FUDDs can support bacterial growth and harbor potential pathogens. Care should be taken to ensure that Servicemembers are aware of the importance of the proper care and cleaning of these devices in the field environment. To this end, standard operating procedures should be developed and distributed.


Sujet(s)
Personnel militaire , Dérivation urinaire , Biofilms , Femelle , Humains , Proteus mirabilis
7.
Infect Drug Resist ; 14: 1-10, 2021.
Article de Anglais | MEDLINE | ID: mdl-33442271

RÉSUMÉ

PURPOSE: The biology of chronic wounds is complex and many factors act concurrently to impede healing progress. In this study, the dynamics of microflora changes and their antibiotic susceptibility patterns were evaluated longitudinally over 30 days using data from 28 patients with a total of 47 chronic lower extremity wounds. MATERIALS AND METHODS: In this study, colonized wound isolates were characterized using cultural, biochemical, and VITEK 2 methods. Antibiotic susceptibility patterns of the wound isolates were analyzed using various phenotypic assays. Furthermore, antimicrobial resistance patterns and the presence of mutations were evaluated by a genotypic assay, whole-genome sequencing (WGS). RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were found to be the most common strains at early time points, while members of Enterobacteriaceae were prevalent at later stages of infection. Antimicrobial resistance testing and whole-genome sequencing revealed that the molecular and phenotypic characteristics of the identified wound pathogens remained relatively stable throughout the study period. It was also noted that Enterobacter and Klebsiella species may serve as reservoirs for quinolone resistance in the Pacific region. CONCLUSION: Our observations showed that wounds were colonized with diverse bacteria and interestingly their numbers and/or types were changed over the course of infection. The rapid genetic changes that accompanied the first 4 weeks after presentation did not directly contribute to the development of antibiotic resistance. In addition, standard wound care procedures did not appear to select for resistant bacterial strains. Future efforts should focus on defining those genetic changes associated with the wound colonizing microorganisms that occur beyond 4 weeks.

8.
J Microbiol Methods ; 169: 105833, 2020 02.
Article de Anglais | MEDLINE | ID: mdl-31904440

RÉSUMÉ

Virulence is the relative capacity of a pathogenic microorganism to cause damage in susceptible host cells such as those found in airway passages and the gut. In this study, the effect of clinical bacterial isolates on the monolayer integrity of cultured human alveolar basal epithelial cells (A549) was evaluated using the Electric Cell-Substrate Impedance Sensing (ECIS) system. ECIS is a morphological biosensor which records electrical properties of cell-covered microelectrodes in an AC circuit including impedance (ohm), resistance (ohm), and capacitance (µFarad). In the current study, fluctuations in the electrical properties of cell-covered microelectrodes reflect dynamic changes in cell morphology resulting from disrupted cell monolayers following exposure to bacteria. Using the ECIS system, real-time changes of cell morphology and disruption of monolayer integrity of cell-cultures in vitro were revealed for A549 cells infected with either Pseudomonas aeruginosa, ESBL Escherichia coli, Staphylococcus aureus (MRSA), or Enterococcus (VRE). We determined empirically that the optimal signal response was obtained for resistance (ohm) measurements at 4000 hertz. Following infection of A549 cells, the data revealed that Pseudomonas aeruginosa resulted in little change in microelectrode resistance (ohm @4 kHz) as compared to pathogen-free controls within the first 12 h. In contrast, E. coli, MRSA, and VRE caused significant changes in electrode resistance (ohm @4 kHz) values in the infected cells compared to controls over the first 5 h. Resistance (ohm @4 kHz) changes were also observed in cell monolayers infected with different bacterial concentrations for all isolates over 24 h. The highest concentration of bacteria caused the measured resistance (ohm @4 kHz) to drop faster than its' immediate lower concentration, suggesting a dose-dependent effect. Compared to live bacteria, cells exposed to heat-killed bacteria did not show significant changes in resistance (ohm @4 kHz) over 48 h post-exposure. Functionally, cytokine responses were different between cells treated with live and heat-killed bacteria. Of note, live bacteria induced IFNγ, IL-13, and IL-1ß production in A549 cells, whereas heat-killed bacteria induced IL-8 production suggesting a differential interaction with cells that could reveal the underlying causes of resistance (ohm @4 kHz) changes. Our findings indicate that ECIS provides a means to quantify, automate, and measure bacterial virulence, which may have broader implications governing the course of treatment compared to traditional methods alone.


Sujet(s)
Bactéries/métabolisme , Phénomènes physiologiques cellulaires/physiologie , Impédance électrique , Cellules épithéliales/microbiologie , Cellules A549 , Techniques de biocapteur/méthodes , Lignée cellulaire , Cytokines/métabolisme , Enterococcus/isolement et purification , Enterococcus/métabolisme , Enterococcus/pathogénicité , Escherichia coli/isolement et purification , Escherichia coli/métabolisme , Escherichia coli/pathogénicité , Humains , Microélectrodes , Pseudomonas aeruginosa/isolement et purification , Pseudomonas aeruginosa/métabolisme , Pseudomonas aeruginosa/pathogénicité , Staphylococcus aureus/isolement et purification , Staphylococcus aureus/métabolisme , Staphylococcus aureus/pathogénicité , Jonctions serrées/microbiologie
9.
J Spec Oper Med ; 19(1): 14-15, 2019.
Article de Anglais | MEDLINE | ID: mdl-30859518

RÉSUMÉ

The genus Acinetobacter has long been associated with war wounds. Indeed, A baumannii was responsible for so many infected wounds during Operation Iraqi Freedom that it was given the nickname "Iraqibacter." Therefore, it is important to monitor the occurrence and spread of Acinetobacter species in military populations and to identify new or unusual sources of infection. A junii is an infrequently reported human pathogen. Here, we report a case of a slow-healing wound infection with A junii in a woman on the island of Oahu. This case highlights the pathogenic potential of this organism and the need for proper wound care when dealing with slow-healing wounds of unknown etiology. It also underscores the need for identifying species of Acinetobacter that are not A baumannii to better understand the epidemiology of slow-healing wound infections.


Sujet(s)
Acinetobacter/isolement et purification , Personnel militaire , Infection de plaie/diagnostic , Infection de plaie/microbiologie , Femelle , Hawaï , Humains , Cicatrisation de plaie
10.
Sci Rep ; 8(1): 11736, 2018 08 06.
Article de Anglais | MEDLINE | ID: mdl-30082843

RÉSUMÉ

Hawaii has one of the highest incidences of Campylobacteriosis in the United States, but there remains little published data on circulating strains or antimicrobial resistance. We characterized 110 clinical Campylobacter isolates (106 C. jejuni, 4 C. coli) processed at Tripler Army Medical Center in Honolulu, HI from 2012-2016. Twenty-five percent of C. jejuni isolates exhibited fluoroquinolone (FQ) resistance, compared with 16% for tetracycline (TET), and 0% for macrolides. Two of the four C. coli isolates were resistant to FQ, TET, and macrolides. C. jejuni isolates further underwent multilocus sequence typing, pulsed-field gel electrophoresis, and molecular capsular typing. Nineteen capsule types were observed, with two capsule types (HS2 and HS9) being associated with FQ resistance (p < 0.001 and p = 0.006, respectively). HS2 FQ-resistant isolates associated with clonal complex 21, possibly indicating clonal spread in FQ resistance. Macrolides should be considered for treatment of suspect cases due to lack of observed resistance.


Sujet(s)
Campylobacter/effets des médicaments et des substances chimiques , Adulte , Antibactériens/pharmacologie , Campylobacter/génétique , Infections à Campylobacter/prévention et contrôle , Résistance bactérienne aux médicaments/génétique , Électrophorèse en champ pulsé , Femelle , Fluoroquinolones/pharmacologie , Hawaï , Humains , Macrolides/pharmacologie , Mâle , Typage par séquençage multilocus , Études rétrospectives , Tétracycline/pharmacologie , Jeune adulte
11.
J Spec Oper Med ; 15(4): 113-116, 2015.
Article de Anglais | MEDLINE | ID: mdl-26630106

RÉSUMÉ

Acute and chronic wound infections can both be encountered in the deployed setting. These wounds are often contaminated by bacteria and fungi derived from the external environment. In this article, we present the case of a wound infection simultaneously colonized by Enterobacter cloacae (a bacterial pathogen) and Trichosporon asahii (an unusual fungal pathogen). We describe the examination and treatment of the patient and review the distinguishing characteristics of each organism.


Sujet(s)
Enterobacter cloacae , Infections à Enterobacteriaceae/complications , Infections à Enterobacteriaceae/diagnostic , Trichosporonose/complications , Trichosporonose/diagnostic , Infection de plaie/traitement médicamenteux , Infection de plaie/microbiologie , Sujet âgé de 80 ans ou plus , Co-infection/microbiologie , Infections à Enterobacteriaceae/traitement médicamenteux , Humains , Traumatismes de la jambe/complications , Mâle , Trichosporon , Trichosporonose/traitement médicamenteux
12.
Hawaii J Med Public Health ; 74(7): 230-3, 2015 Jul.
Article de Anglais | MEDLINE | ID: mdl-26225268

RÉSUMÉ

Bordetella bronchiseptica (B. bronchiseptica) is rarely implicated in human disease. Human infections typically occur in the context of immunosuppression and while human infection has been sporadically reported in the literature, the majority of these reports are largely descriptive and do not explore the molecular and phenotypic properties of the isolates in question. Here we report the isolation and characterization of a B. bronchiseptica isolate derived from an HIV positive patient at Tripler Army Medical Center on O'ahu. This case represents the first published report of human infection of B. bronchiseptica in the state of Hawai'i and the most detailed description of the biochemical and molecular features of a Hawaiian isolate to date.


Sujet(s)
Infections opportunistes liées au SIDA/microbiologie , Bordetelloses/microbiologie , Bordetella bronchiseptica/isolement et purification , Bordetella bronchiseptica/métabolisme , Dyspnée/microbiologie , Hawaï , Hôpitaux militaires , Humains , Mâle , Adulte d'âge moyen , Typage moléculaire , Phénotype , Insuffisance respiratoire/microbiologie
13.
Mil Med ; 179(4): 445-50, 2014 Apr.
Article de Anglais | MEDLINE | ID: mdl-24690971

RÉSUMÉ

Staphylococcus aureus (S. aureus) is a major cause of morbidity in the military health care setting. Culture-based methods are the most common means of identifying infections caused by this agent. However, culture-based methods lack sensitivity and specificity. The Abbott PLEX-ID instrument uses a combination of the polymerase chain reaction and mass spectrometry for the identification of bacterial isolates. We investigated whether the Abbott PLEX-ID system could identify S. aureus in clinical material and facilitate the epidemiological analysis of individual isolates. The PLEX-ID system positively identified 100% of isolates previously found to be methicillin resistant S. aureus by culture. In addition, analysis using the PLEX-ID software revealed that the majority of S. aureus isolates at Tripler Army Medical Center derive from clonal complex 8 and nearly 100% of these strains express the R-variant of the Panton-Valentine leukocidin virulence factor. These results demonstrate the utility of the PLEX-ID system in identifying clinical isolates and reveal an unexpected level of homogeneity among clinical S. aureus isolates recovered at Tripler Army Medical Center. These results also demonstrate the utility of the PLEX-ID system in identifying the resistance patterns, predicting the virulence properties, and tracking the migration of bacterial pathogens in the clinical setting.


Sujet(s)
Hôpitaux militaires , Spectrométrie de masse/instrumentation , Staphylococcus aureus résistant à la méticilline/génétique , Personnel militaire , Réaction de polymérisation en chaîne/méthodes , Infections à staphylocoques/microbiologie , Humains , Infections à staphylocoques/diagnostic
14.
J Cell Biochem ; 91(4): 808-20, 2004 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-14991772

RÉSUMÉ

TRPV ion channels transduce a range of temperature stimuli. We proposed that analysis of the protein-protein interactions made by TRPV2 might give insight into the key issues surrounding this channel. These issues include the potential functional significance of TRPV2 in non-sensory tissues, the molecules involved in transducing its activation signal(s) and the mechanism by which its trafficking to the cell surface is regulated. Here we describe the interaction of TRPV2 channel with the RGA gene product. RGA is a four-transmembrane domain, intracellularly localized protein. RGA associates with TRPV2 in a rat mast cell line that is a native context for both proteins. The interaction between TRPV2 and RGA is transient and occurs intracellularly. RGA does not accompany TRPV2 to the cell surface. Formation of the TRPV2/RGA complex is dependent upon a cellular glycosylation event, suggesting that RGA may play a chaperone or targeting role for TRPV2 during the maturation of the ion channel protein. These data record a novel protein-protein interaction for TRPV2 and provide a foundation for future study of the potential regulatory contribution of RGA to TRPV2 function.


Sujet(s)
Canaux ioniques/métabolisme , Protéines membranaires/métabolisme , Récepteurs des médicaments/métabolisme , Animaux , Lignée cellulaire , Membrane cellulaire/métabolisme , Cytoplasme/métabolisme , Humains , Immunoprécipitation , Canaux ioniques/génétique , Protéines membranaires/biosynthèse , Protéines membranaires/composition chimique , Protéines membranaires/génétique , Souris , Microscopie de fluorescence , Données de séquences moléculaires , Phylogenèse , Liaison aux protéines/effets des médicaments et des substances chimiques , Transport des protéines , ARN messager/génétique , ARN messager/métabolisme , Rats , Récepteurs des médicaments/génétique , Analyse de séquence de protéine , Canaux cationiques TRPV , Tunicamycine/pharmacologie , Techniques de double hybride
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