Archive for the 'Phage therapy' Category

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium: A Model for Phage Therapy of Intracellular Bacterial Pathogens

January 12, 2017
Lawrence Broxmeyer, Danuta Sosnowska, Elizabeth Miltner, Ofelia Chacon, Dirk Wagner, Jeffery McGarvey, Raul G. Barletta, and Luiz E. Bermudez

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage

The Journal of Infectious Diseases

ABSTRACT

Mycobacterium avium causes disseminated infection in patients with acquired immune deficieny syndrome. Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually. Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages. These results showed that treatment of M. avium–infected, as well as M. tuberculosis –infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time and titer  dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fuses with the M. avium vacuole in macrophages. These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.

REFERENCES
1. Bloom B. Tuberculosis: pathogenesis, protection and control. Washington,DC: American Society for Microbiology Press, 1995.
2. Surveillance TWIGP. Anti-tuberculosis drug resistance in the world. Geneva:World Health Organization Global Tuberculosis Programme, 1997.
3. Inderlied CB, Kemper CA, Bermudez LE. The Mycobacterium avium complex. Clin Microbiol Rev 1993; 6:266–310.
4. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853–60.
5. Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus–associated opportunistic infections in the United
States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000 ; 30(Suppl 1):S5–14.
6. Falkinham JO 3rd. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996; 9:177–215.
7. Guthertz LS, Damsker B, Bottone EJ, Ford EG, Midura TF, Janda JM. Mycobacterium avium and Mycobacterium intracellulare infections in patients with and without AIDS. J Infect Dis 1989; 160:1037–41.
8. Heifets L. Susceptibility testing of Mycobacterium avium complex isolates. Antimicrob Agents Chemother 1996; 40:1759–67.
9. Horsburgh CR Jr. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324:1332–8.
10. Chaisson RE, Benson CA, Dube MP, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease: a randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med 1994; 121:905–11.
11. Young LS, Wiviott L, Wu M, Kolonoski P, Bolan R, Inderlied CB. Azithromycin for treatment of Mycobacterium avium–intracellulare complex infection in patients with AIDS. Lancet 1991; 338:1107–9.
12. Bermudez LE, Kolonoski P, Young LS. Roxithromycin alone and in combination with either ethambutol or levofloxacin for disseminated Mycobacterium avium infections in beige mice. Antimicrob Agents Chemother 1996; 40:1033–5.
13. Dube MP, Sattler FR, Torriani FJ, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis 1997; 176:1225–32.
14. Holzman D. Phage as antibacterial tool. Genetic Engineering News 1998; 18:11–16.
15. Ford ME, Stenstrom C, Hendrix RW, Hatfull GF. Mycobacteriophage TM4: genome structure and gene expression. Tuber Lung Dis 1998; 79:63–73.
16. Foley-Thomas EM, Whipple DL, Bermudez LE, Barletta RG. Phage infection,transfection and transformation of Mycobacterium avium complex and Mycobacterium paratuberculosis. Microbiology 1995; 141:1173–81.
17. Bermudez LE, Parker A, Goodman JR. Growth within macrophages increases the efficiency of Mycobacterium avium in invading other macrophages by a complement receptor–independent pathway. Infect Immun 1997; 65:1916–25.
18. Jacobs WR Jr, Kalpana GV, Cirillo JD, et al. Genetic systems for mycobacteria. Methods Enzymol 1991; 204:537–55.
19. Black CM, Bermudez LE, Young LS, Remington JS. Coinfection of macrophages modulates interferon gamma and tumor necrosis factor–induced activation against intracellular pathogens. J Exp Med 1990; 172:977–80.
20. Hafner R, Inderlied CB, Peterson DM, et al. Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection. J Infect Dis 1999; 180:438–47.
21. Sula L, Sulova J, Stolcpartova M. Therapy of experimental tuberculosis in guinea pigs with mycobacterial phages DS-6A, GR-21 T, My-327. Czech Med 1981; 4:209–14.
22. Rastogi N, Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother 1991; 35:462–70.
23. Bermudez LE, Young LS. New drugs for the therapy of mycobacterial infections. Curr Opinion Infect Dis 1995; 8:428–38.
24. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 1994; 263:678–81.
25. Clemens DL, Horwitz MA. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 1995
; 181:257–70.
26. de Chastellier C, Lang T, Thilo L. Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in comparison to phagosomes which contain Bacillus subtilis or latex beads. Eur J Cell Biol 1995; 68:167–82.
27. Gomes MS, Paul S, Moreira AL, Appelberg R, Rabinovitch M, Kaplan G. Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages. Infect Immun 1999; 67:3199–206.
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Lawrence Broxmeyer, MD

August 14, 2012

Find peer-reviewed papers and other articles from Lawrence Broxmeyer, MD. Broxmeyer addresses some of the most complex medical conditions of our time including AIDS, autism, infuenza, cancer,Parkinson’s, Alzheimer’s Disease, mad cow disease, phage therapy, Jakob-Cruezfeldt, and tuberculosis.

Pennsylvania internist Lawrence Broxmeyer, M.D. has been in various peer-reviewed publications and served as the lead investigator in an important 2002 Journal of Infectious Diseases study dealing with killing mycobacteria in the blood of patients with AIDS.  Broxmeyer’s articles cover a wide spectrum of today’s most complex medical conditions, among them AIDS, cancer, bovine spongiform encephalopathy (mad cow disease), Parkinson’s disease, tuberculosis (TB), Creutzfeldt-Jakob disease, and Alzheimer’s disease. His research is both plausible and well-documented.

Dr. Broxmeyer conducted in depth investigations into the underlying cause of AIDS as well as into whether cancer isn’t actually an incurable infectious disease. He has also established a common thread in the etiology or cause between Alzheimer’s, Creutzfeldt-Jakob,  and mad cow disease. Their etiologies cause-wise are striking. In 2008. Broxmeyer was invited by Landes Bioscience to publish a chapter dealing with novel approaches to control intracellular pathogens in their textbook Patho-Biotechnology.

Dr. Lawrence Broxmeyer currently holds the position of Medical Investigator in Whitestone, New York, at the N.Y. Institute of Research. His team conducts research regarding Parkinson’s disease, AIDS, Alzheimer’s disease, cancer, and the application of phagotherapy, which deals with using bacterial viruses to kill host bacteria. Lawrence Broxmeyer, M.D. brings to his work both  extensive experience in scientific research techniques, as well as his many years as a practicing internist.

Before becoming the founder and Medical Investigator of The N.Y. Institute of Research , Lawrence Broxmeyer, MD served on the staff of several prominent New York affiliate hospitals. As America’s AIDS epidemic progressed, Broxmeyer worked with a teams in San Francisco and at the University of Nebraska Medical Center to research and develop a novel treatment, including an innovative technique for eliminating  immunosuppressive AIDS mycobacteria.

Books written by Lawrence Broxmeyer MD:

Lawrence Broxmeyer, M.D.
Parkinson’s: Another Look
New Century Press, 2002 pp. 82
ISBN: 1890035262, 9781890035266

Dr. Lawrence Broxmeyer MD
AIDS: What the Discoverers of HIV Never Admitted
3rd Edition New Century Press, 2003 pp. 81
ISBN: 1890035297, 9781890035297

Textbooks and Periodicals in which Lawrence Broxmeyer M.D. appeared in:

Lawrence Broxmeyer, MD; Phage Therapy: A Trojan Horse Approach to the Control of Intracellular Pathogens; In Patho-Biotechnology Eds Roy Sleator and Colin Hill Landes Bioscience July 2008 pp. 238. 41-49

Lawrence Broxmeyer, M.D. The Untold Truth about Cancer- Pts 1 and 2 Nexus Vol 17 No 1-No2  Dec 2009-Jan 2010 pp35-40; February-March 2010 pp.37-42.

Medline Publications of Dr. Lawrence Broxmeyer as listed in
The U.S. National Library of Medicine, National Institutes of Health:

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens.
Lawrence Broxmeyer MD, Sosnowska D, Miltner E, Chacón O, Wagner D, McGarvey J, Barletta RG, Bermudez LE.
Journal of Infectious Diseases. 2002 Oct 15;186(8):1155-60. Epub 2002 Sep 30.PMID: 12355367 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Is cancer just an incurable infectious disease?
Dr. Lawrence Broxmeyer M.D.
Med Hypotheses. 2004;63(6):986-96.PMID: 15504566 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Is mad cow disease caused by a bacteria?
Lawrence Broxmeyer, MD
Med Hypotheses. 2004;63(4):731-9.PMID: 15325025 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Bacteriophages: antibacterials with a future?
Lawrence Broxmeyer, M.D.
Med Hypotheses. 2004;62(6):889-93.PMID: 15142642 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Heart disease: the greatest ‘risk’ factor of them all.
Lawrence Broxmeyer, MD
Med Hypotheses. 2004;62(5):773-9.PMID: 15082105 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

SARS: just another viral acronym?
Lawrence Broxmeyer, M.D.
Med Hypotheses. 2003 Aug;61(2):314-7.PMID: 12888325 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Is AIDS really caused by a virus?
Lawrence Broxmeyer, MD
Med Hypotheses. 2003 May;60(5):671-88. No abstract available. PMID: 12710902 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

Parkinson’s: another look.
Lawrence Broxmeyer M.D.
Med Hypotheses. 2002 Oct;59(4):373-7.PMID: 12208174 [PubMed – indexed for MEDLINE][Link-out to article on lawrencebroxmeyermd.com]

AIDS: “it’s the bacteria, stupid!”.
Lawrence Broxmeyer, MD, Dr. Alan Cantwell, MD
Med Hypotheses. 2008 Nov;71(5):741-8. Epub 2008 Aug 8. [Link-out to article on lawrencebroxmeyermd.com]

Bird flu, influenza and 1918: the case for mutant Avian tuberculosis.
Dr. Lawrence Broxmeyer M.D.
Med Hypotheses. 2006;67(5):1006-15. Epub 2006 Jun 27. [Link-out to article on lawrencebroxmeyermd.com]

Diabetes mellitus, tuberculosis and the mycobacteria: two millenia of enigma.
Lawrence Broxmeyer MD
Med Hypotheses. 2005;65(3):433-9 [Link-out to article on lawrencebroxmeyermd.com]

Thinking the unthinkable: Alzheimer’s, Creutzfeldt-Jakob and Mad Cow disease: the age-related reemergence of virulent, foodborne, bovine tuberculosis or losing your mind for the sake of a shake or burger.
Lawrence Broxmeyer M.D.
Med Hypotheses. 2005;64(4):699-705.PMID: 15694685 [PubMed – indexed for MEDLINE] [Link-out to article on lawrencebroxmeyermd.com]

 

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Hello world!

August 14, 2012

These are the manuscripts, thoughts and laboratory results of physician/researcher Lawrence Broxmeyer, M.D.. As a medical investigator and author, his mission is and has always been to push out the boundaries of what is known towards those of what is conceivable. What he writes, along a historical time-frame is both compelling and well-documented addressing some of the most challenging problems in medicine today, among them AIDS, Alzheimer’s disease, Parkinson’s disease, autism, cancer, diabetes, heart disease, HIV, influenza, the Pandemic of 1918, TSE, the Transmissible Spongioform Encephalopathies, tuberculosis, Jakob-Cruezfeldt disease, mad-cow disease, phage therapy and recent mycobacterial research.  If you are expecting to read the parroting of present medical orthodoxy, you might be disappointed. If on the other hand, you are not entirely satisfied with certain areas of present day dogma and the results they bring, you might find Broxmeyer’s ideas absorbing. Anyway, let us begin………….