Link Between Bacteria and Blood Cancer

Learn more about the Paenibacillus species strain VT 400

Bacterial cultures being grown on different culture media.

In the summer of 2016, at the annual meeting of the American Society for Microbiology, scientists gathered to share and discuss findings related to the world of bacteria and human health.

Among the discoveries, a group reported on the entire genome, or the complete set of genes, for a bacterium called Paenibacillus species strain VT 400 (PVT400). These bacteria had been previously found in the saliva of a pediatric patient with acute lymphoblastic leukemia (ALL).

The detailed information from this and future studies will help scientists learn whether these bacteria may have a role in human disease, especially in people with acute leukemia who develop pneumonia or bloodstream infections.

Pneumonia in People With Cancer

Pneumonia is the leading cause of death in cancer patients with neutropenia, and particularly those with acute leukemia. Neutropenia is a low count of neutrophils in the blood—neutrophils are white blood cells that are important in helping the body to fight infection.

Lower respiratory tract infections are very common among cancer patients, with some reports showing that 13 to 31 percent of leukemia patients receiving chemotherapy and up to 80 percent of hematopoietic stem cell transplant recipients will experience at least one episode of pneumonia.

Neutropenic pneumonias are potentially life-threatening infections. In such scenarios, doctors start antibiotic therapy immediately, without waiting for laboratory results to confirm and specify the type of bacterial infection—because it is so important to start treatment at once, to reduce the risk that the patient will succumb to the infection.

In fact, preventive therapy is used in certain circumstances, which are detailed below.

Recent advances in the management of neutropenic pneumonia are spurring hope for better outcomes. Multiple medical societies have issued updated guidelines for antibiotic therapy of suspected neutropenic pneumonia.

And it is possible that newer agents that promote the body’s responses to infection may further enhance the activity of antibiotics.

Focusing on the Pathogens in Patients With Neutropenia

Guidelines from the American Society of Clinical Oncology (ASCO) recommend that physicians attempt to prevent infection in outpatients with profound neutropenia but no fever. Antibacterial and antifungal treatment is advised if neutrophils are expected to remain below 100/µL for more than seven days. The guideline states that the preferable agent for antibacterial preventive therapy is an oral fluoroquinolone, while that for antifungal therapy is an oral triazole.

Patients with neutropenia are susceptible to a much broader variety of pathogens than their counterparts. It can be helpful for doctors to consider where the bacteria came from in predicting which antibiotics they are likely to be resistant to, and therefore which strategies are most likely to be most effective.

Paenibacillus Species

Toward that end, scientists have been studying PVT400, the new bacteria isolated from the leukemia patient, a member of the Paenibacillus genus—a family of rod-shaped bacterial species.

Different species within this group have been isolated from soil, water, plants, milk, and other sites. However, Paenibacillus species were not known to cause human disease... until recent reports showed the possible involvement of three different Paenibacillus species in human diseases.

After PVT 400 was isolated from the saliva of a pediatric patient with acute lymphoblastic leukemia, early studies showed some similarity of these isolates with the amylolyticus species, which is found in the larval hindgut of the fly; however, to date, it is still true that P. amylolyticus has not been detected in humans, and further studies showed differences between the strain-VT 400 bacteria found in the cancer patient and other P. amylolyticus strains.

So, when investigators studied the entire VT 400 genome, there where a number of interesting findings. It had genes encoding resistance mechanisms to chemotherapy drugs, like tunicamycin and bleomycin. They also found genes for bacterial pumps associated with multidrug resistance, as well as genes encoding resistance to antibiotics, including vancomycin, fosmidomycin, tetracycline as well as penicillin-like drugs, or the beta lactams.

The authors of this genome-study noted that the complete genome sequence of Paenibacillus sp. strain VT 400 will help determine the role of Paenibacillus species in human diseases and provide insights into the composition of the normal bacteria living in patients with blood cancers.

Sources:

Evans SE, Ost DE. Pneumonia in the neutropenic cancer patient. Curr Opin Pulm Med. 2015;21(3):260-271.

Rybakova D, Wetzlinger U, Müller H, et al. Complete genome sequence of Paenibacillus polymyxa strain SB3-1, a soilborne bacterium with antagonistic activity toward plant pathogens. Genome Announc. 2015;3(2):e00052-15.

De Souza R, Sant’Anna FH, Ambrosini A, et al. Genome of Pseudomonas sp. FeS53a, a putative plant growth-promoting bacterium associated with rice grown in iron-stressed soils. Genome Announc. 2015;(2):e00248-15. 10.1128/genomeA.00248-15.

Spence R, Demchick P, Hornitzky M, et al. Surveillance of New Zealand apiaries for Paenibacillus alvei. N Z Entomol. 2013;36:82–86.

Kim KK, Lee KC, Yu H, et al. Paenibacillus sputi sp. nov., isolated from the sputum of a patient with pulmonary disease. Int J Syst Evol Microbiol. 2010;60:2371–2376.

Mulcahy N. New ASCO Guideline on neutropenia and fever. Medscape Medical News. Jan 16 2013. Available at http://www.medscape.com/viewarticle/777736.

Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013; 31(6):794-810.

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