Bacteria in Cancer Therapeutics: A Framework for Effective Therapeutic Bacterial Screening and Identification.

By 2030, the global incidence of cancer is expected to increase by approximately 50%. However, most conventional therapies still lack cancer selectivity, which can have severe unintended side effects on healthy body tissue. Despite being an unconventional and contentious therapy, the last two decades have seen a significant renaissance of bacterium-mediated cancer therapy (BMCT). Although promising, most present-day therapeutic bacterial candidates have not shown satisfactory efficacy, effectiveness, or safety. Furthermore, therapeutic bacterial candidates are available to only a few of the approximately 200 existing cancer types. Excitingly, the recent surge in BMCT has piqued the interest of non-BMCT microbiologists. To help advance these interests, in this paper we reviewed important aspects of cancer, present-day cancer treatments, and historical aspects of BMCT. Here, we provided a four-step framework that can be used in screening and identifying bacteria with cancer therapeutic potential, including those that are uncultivable. Systematic methodologies such as the ones suggested here could prove valuable to new BMCT researchers, including experienced non-BMCT researchers in possession of extensive knowledge and resources of bacterial genomics. Lastly, our analyses highlight the need to establish and standardize quantitative methods that can be used to identify and compare bacteria with important cancer therapeutic traits.

Widespread amphotericin B-resistant strains of Aspergillus fumigatus in Hamilton, Canada.

PURPOSE: Amphotericin B (AMB) is one of the major antifungal drugs used in the management of aspergillosis and is especially recommended for treating triazole-resistant strains of Aspergillus fumigatus. However, relatively little is known about the AMB susceptibility patterns of A. fumigatus in many parts of the world. This study aims to describe the AMB susceptibility patterns in Hamilton, Ontario, Canada. METHODS: The in vitro susceptibilities of 195 environmental and clinical A. fumigatus isolates to AMB were tested by the broth microdilution method as per the Clinical and Laboratory Standards Institute's guidelines. Catalase-generated oxygen bubbles trapped by Triton X-100 were used to quantify catalase activity in a representative group of isolates. RESULTS: Of the 195 isolates, 188 (96.4%) had the minimum inhibitory concentration (MIC) of AMB ≥2 mg/L, with approximately 80% and 20% of all clinical and environmental isolates having MICs of ≥ 4 mg/L. Overall, the clinical isolates were less susceptible to AMB than environmental isolates (P-value <0.001). The strain with the highest AMB MIC (16 mg/L) had one of the highest catalase activities. However, there was no correlation between AMB MIC and catalase activity in our sample. CONCLUSION: The widespread AMB resistance suggests that using AMB in the management of A. fumigatus infections in Hamilton would likely result in treatment failure. Although high catalase activity may have contributed to AMB resistance in some isolates, the mechanism(s) for the observed AMB resistance in Hamilton is unknown and likely complex.

Strengthening the One Health Agenda: The Role of Molecular Epidemiology in Aspergillus Threat Management.

The United Nations' One Health initiative advocates the collaboration of multiple sectors within the global and local health authorities toward the goal of better public health management outcomes. The emerging global health threat posed by Aspergillus species is an example of a management challenge that would benefit from the One Health approach. In this paper, we explore the potential role of molecular epidemiology in Aspergillus threat management and strengthening of the One Health initiative. Effective management of Aspergillus at a public health level requires the development of rapid and accurate diagnostic tools to not only identify the infecting pathogen to species level, but also to the level of individual genotype, including drug susceptibility patterns. While a variety of molecular methods have been developed for Aspergillus diagnosis, their use at below-species level in clinical settings has been very limited, especially in resource-poor countries and regions. Here we provide a framework for Aspergillus threat management and describe how molecular epidemiology and experimental evolution methods could be used for predicting resistance through drug exposure. Our analyses highlight the need for standardization of loci and methods used for molecular diagnostics, and surveillance across Aspergillus species and geographic regions. Such standardization will enable comparisons at national and global levels and through the One Health approach, strengthen Aspergillus threat management efforts.

Evidence of unique genetic diversity in Aspergillus fumigatus isolates from Cameroon.

Aspergillus fumigatus is a saprophytic fungus that can cause lethal invasive aspergillosis in immunocompromised patients. Recent studies have shown that Eurasian and North American populations of A. fumigatus often consist of genetically diverse strains. However, very little is known about African populations of A. fumigatus. Here, we characterise the genetic diversity and triazole susceptibility of A. fumigatus in Cameroon, West Africa. A total of 495 soil samples were obtained from nine collection sites in three Cameroonian regions. Nine microsatellite markers were used to genotype all 51 identified A. fumigatus isolates. In vitro susceptibility to itraconazole and voriconazole was tested using micro broth dilution. The 51 Cameroonian A. fumigatus isolates belonged to 45 genotypes. Consistent with recombination, 32 of 36 possible pairwise loci combinations are phylogenetically incompatible. Interestingly, evidence for geographic sub-structuring was found within Cameroon and the sub-population with the most evidence of recombination was also the least susceptible sub-population to the triazole antifungals tested. Furthermore, the Cameroonian sample was significantly differentiated from those in Eurasia and North America. Overall, our results indicate the genetic uniqueness of Cameroonian A. fumigatus populations and that additional novel genetic diversity likely exist in other parts of Africa.

Emigration of skilled healthcare workers from developing countries: can team-based healthcare practice fill the gaps in maternal, newborn and child healthcare delivery?

BACKGROUND AND INTRODUCTION: Emigration of healthcare workers from developing countries is on the rise and there is an urgent need for policies that increase access to and continuity of healthcare. In this commentary, we highlight some of the negative impacts of emigration on maternal and child health and discuss whether team-based healthcare delivery could possibly mitigate the shortfall of maternal and child health professionals in developing countries. METHODOLOGY: We cross-examine the availability of supporting structures to implement team-based maternal and child healthcare delivery in developing countries. We briefly discuss three key supporting structures: culture of sharing, telecommunication, and inter-professional education. Supporting structures are examined at system, organizational and individual levels. We argue that the culture of sharing, limited barriers to inter-professional education and increasing access to telecommunication will be advantageous to implementing team-based healthcare delivery in developing countries. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Although most developing countries may have notable supporting structures to implement team-based healthcare delivery, the effectiveness of such models in terms of cost, time and infrastructure in resource limited settings is still to be evaluated. Hence, we call on usual stakeholders, government, regulatory colleges and professional associations in countries with longstanding emigration of maternal and child healthcare workers to invest in establishing comprehensive models needed to guide the development, implementation and evaluation of team-based maternal and child healthcare delivery.

Population structure, epidemiology and antibiotic resistance patterns of Streptococcus pneumoniae serotype 5: prior to PCV-13 vaccine introduction in Eastern Gambia.

BACKGROUND: Streptococcus pneumoniae serotype 5 is among the most common serotypes causing invasive pneumococcal disease (IPD) in The Gambia. We anticipate that introduction of the 13-valent pneumococcal conjugate vaccine (PCV-13) into routine vaccination in The Gambia will reduce serotype 5 IPD. However, the emergence of new clones that have altered their genetic repertoire through capsular switching or genetic recombination after vaccination with PCV-13 poses a threat to this public health effort. In order to monitor for potential genetic changes post-PCV-13 vaccination, we established the baseline population structure, epidemiology, and antibiotic resistance patterns of serotype 5 before the introduction of PCV-13. METHODS: Fifty-five invasive S. pneumoniae serotype 5 isolates were recovered from January 2009 to August 2011 in a population-based study in the Upper River Region of The Gambia. Serotyping was done by latex agglutination and confirmed by serotype-specific Polymerase Chain Reaction (PCR). Genotyping was undertaken using Multilocus Sequence Typing (MLST). Antimicrobial sensitivity was done using disc diffusion. Contingency table analyses were conducted using Pearson's Chi(2) and Fisher's exact test. Clustering was performed using Bionumerics version 6.5. RESULTS: MLST resolved S. pneumoniae serotype 5 isolates into 3 sequence types (ST), namely ST 289(6/55), ST 3339(19/55) and ST 3404(30/55). ST 289 was identified as the major clonal complex. ST 3339, the prevalent genotype in 2009 [84.6% (11/13)], was replaced by ST 3404 [70.4% (19/27)] in 2010 as the dominant ST. Interestingly, ST 3404 showed lower resistance to tetracycline and oxacillin (P < 0.001), an empirical surrogate to penicillin in The Gambia. CONCLUSIONS: There has been an emergence of ST 3404 in The Gambia prior to the introduction of PCV-13. Our findings provide important background data for future assessment of the impact of PCV-13 into routine immunization in developing countries, such as The Gambia.