Cancer research

Cancer has a major impact on human society worldwide, leading to a significant reduction in life expectancy. According to data published by the Centers for Disease Control (CDC) in 2015, it is estimated that greater than 1.6 million new cases of cancer will be diagnosed in the US each year, resulting in greater than 0.5 million deaths. The predominant forms of cancer include breast, lung, and prostate cancer, and malignancies of the gastrointestinal tract. With the exception of germline DNA mutations, which have been attributed to malignization, little is known regarding the direct causes of cancers.

The founders of the Human Microbiology Institute, we have made groundbreaking discoveries that establish new links between the human microbiome and cancer development and progression. We believe that these discoveries will ultimately result in the development of novel cancer therapeutics.

PRIMARY DIRECTIONS OF THE RESEARCH

Novel Pathogens Search

Using unique methods developed by HMI scientists, we are endeavoring to evaluate the particularities of the microbiota among cancer patients and to better understand the role of the microbiota in both carcinogenicity and in the efficacy of cancer treatment. This issue is particularly relevant given our current inability to identify all causative agents of pathological processes, as bacterial infections comprise one of the primary causes of treatment failure and death among cancer-induced immunosuppressed patients. More importantly, however, certain bacterial species also play a direct role in the malignization of certain types of cancers. As such, these cancers could be considered bacteria-related diseases. Indeed, it is estimated that greater than 20% of cancers (which is likely an underestimation) are caused by microbes or are microbe-related.

The founders have  already identified several novel bacterial species and have made amazing breakthroughs  regarding the role of these organisms in hematological malignancies and in patients with gastrointestinal cancer. HMI’s future work is aimed at continuing and expanding on these studies.

The scope of our microbiota-related cancer research includes the following cancer types:

  • Breast cancer
  • Colon cancer
  • Gastric cancer
  • Esophageal cancer
  • Kidney cancer
  • Melanoma
  • Multiple myeloma
  • Leukemia (acute lymphocytic leukemia; acute myeloid leukemia; chronic lymphocytic leukemia; chronic myeloid leukemia; chronic myelomonocytic leukemia)
  • Lung cancer
  • Lymphoma
  • Ovarian cancer
  • Pancreatic cancer
  • Prostate cancer

 

Novel Therapeutic Directions

HMI-M-TRANSPLANTAT (NEW GENERATION OF MICROBIOTA TRANSPLANTATION)

The HMI is currently developing a unique therapy that is based on unanticipated results obtained from a study of distinct mechanisms of cooperation between the microbiota and mitochondria, named “HMI-M-Transplantat”. This therapeutic solution for the first time takes into consideration the unexpected link between the microbiota and the host organism, and is based on the Tetz’s Theory of longevity, maternal inheritance of microbiota, diseases of the microbiota, and the Pangenome concept. Moreover, the HMI is developing individualized algorithms for the usage of this unique product to prevent and overcome certain types of cancers.

RecD1

HMI scientists are currently developing a new compound that exhibits multipotent targeting. Using this compound, it may be possible to substantially inhibit tumor development and prevent tumor metastasis.

NT-49

The HMI has identified a new group of potential therapeutic targets. By targeting these factors, it may be possible to slow tumor development and metastasis, as well as the development cachexia. Moreover, our findings have resulted in the development of a first-in-class, potentially groundbreaking, therapeutic solution named NT-49, which is currently under intensive study at the HMI.

The Human Microbiology Institute is dedicated to collaborate with other research organizations and entities involved in this field. To that end the HMI will develop means by which to make the results of this research widely available on a non- discriminatory basis.

Publications:
  1. Genomic characterization and assessment of the virulence and antibiotic resistance of the novel species Paenibacillus sp. strain VT-400, a potentially pathogenic bacterium in the oral cavity of patients with hematological malignancies
    Gut pathogens (2016)
  2. Complete Genome Sequence of Paenibacillus sp. Strain VT-400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia.
    Genome announcements (2015)
  3. Complete Genome Sequence of Paenibacillus sp. Strain VT-400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia.
    Genome announcements (2015)
  4. Complete Genome Sequence of Bacilli bacterium Strain VT-13-104 Isolated from the Intestine of a Patient with Duodenal Cancer.
    Genome announcements (2015)
  5. Complete Genome Sequence of the Streptococcus sp. Strain VT 162, Isolated from the Saliva of Pediatric Oncohematology Patients.
    Genome announcements (2014)

 

Complete Genome Sequence of Paenibacillus sp. strain VT-400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia

Genome announcements (2015)

Complete Genome Sequence of Paenibacillus sp. strain VT-400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia

Publication Type Journal Article
Authors George Tetz

Victor Tetz

Maria Vecherkovskaya

Abstract We report here the complete genome sequence of spore-forming Paenibacillus sp. strain VT 400, isolated from the saliva of a child with acute lymphoblastic leukemia. The genome consists of 6,986,122 bp, with a G+C content of 45.8%. It possesses 5,777 predicted protein-coding genes encoding multidrug resistance transporters, virulence factors, and resistance to chemotherapeutic drugs.
Year of Publication 2015
Journal Genome announcements
DOI 10.1128/genomeA.00894-15

Genomic characterization and assessment of the virulence and antibiotic resistance of the novel species Paenibacillus sp. strain VT-400, a potentially pathogenic bacterium in the oral cavity of patients with hematological malignancies

Publication Type Journal Article
Authors George Tetz

Victor Tetz

Maria Vecherkovskaya

Abstract Background

Paenibacillus sp. strain VT-400, a novel spore-forming bacterium, was isolated from patients with hematological malignancies.

Methods

Paenibacillus sp. strain VT-400 was isolated from the saliva of four children with acute lymphoblastic leukemia. The genome was annotated using RAST and the NCBI Prokaryotic Genome Annotation Pipeline to characterize features of antibiotic resistance and virulence factors. Susceptibility to antibiotics was determined by the Kirby–Bauer disc diffusion method. We used a mouse model of pneumonia to study virulence in vivo. Mice were challenged with 7.5 log10–9.5 log10 CFU, and survival was monitored over 7 days. Bacterial load was measured in the lungs and spleen of surviving mice 48 h post-infection to reveal bacterial invasion and dissemination.

Results

Whole-genome sequencing revealed a large number of virulence factors such as hemolysin D and CD4+ T cell-stimulating antigen. Furthermore, the strain harbors numerous antibiotic resistance genes, including small multidrug resistance proteins, which have never been previously found in the Paenibacillus genus. We then compared the presence of antibiotic resistance genes against results from antibiotic susceptibility testing. Paenibacillus sp. strain VT-400 was found to be resistant to macrolides such as erythromycin and azithromycin, as well as to chloramphenicol and trimethoprim–sulphamethoxazole. Finally, the isolate caused mortality in mice infected with ≥8.5 log10 CFU.

Conclusions

Based on our results and on the available literature, there is yet no strong evidence that shows Paenibacillus species as an opportunistic pathogen in immunocompromised patients. However, the presence of spore-forming bacteria with virulence and antibiotic resistance genes in such patients warrants special attention because infections caused by spore-forming bacteria are poorly treatable.

Year of Publication 2016
Journal Gut Pathogens
DOI 10.1186/s13099-016-0089-1

Complete Genome Sequence of the Streptococcus sp. strain VT-162, Isolated from the Saliva of Pediatric Oncohematology Patients

Publication Type Journal Article
Authors George Tetz

Maria F. Vecherkovskaya

Victor Tetz

Abstract Streptococcus sp. strain VT 162 was isolated from the saliva of pediatric oncohematology patients. Its full genome is 2,045,418 bp. The availability of this genome will provide insights into the composition of microbial flora among pediatric oncohematology patients and the host interaction and pathogenicity of this species.
Year of Publication 2014
Journal Genome announcements
DOI 10.1128/genomeA.00647-14

Complete genome sequence of Bacilli bacterium strain VT-13-104 isolated from the intestine of a patient with duodenal cancer.

Publication Type Journal Article
Authors George Tetz

Victor Tetz

Abstract We report the complete genome sequence of Bacilli bacterium strain VT-13-104 isolated from the intestine of a patient with duodenal cancer. The genome is composed of 3,573,421 bp, with a G+C content of 35.7%. It possesses 3,254 predicted protein-coding genes encoding multidrug resistance transporters, resistance to antibiotics, and virulence factors.
Year of Publication 2015
Journal Genome announcements
DOI 10.1128/genomeA.00705-15

Draft Genome Sequence of Acinetobacter sp. strain VT-511 Isolated from the Stomach of a Patient with Gastric Cancer

Publication Type Journal Article
Authors George Tetz

Victor Tetz

Abstract We report the draft genome sequence of Acinetobacter sp. strain VT-511, which was obtained from the stomach of a patient with gastric cancer. The genome of Acinetobacter sp. VT-511 is composed of approximately 3,416,321 bp and includes 3,214 predicted protein-coding genes.
Year of Publication 2015
Journal Genome announcements
DOI 10.1128/genomeA.01202-15