Michael Strong

Tuberculosis drug resistance mutation database.

Andreas Sandgren and colleagues describe a new comprehensive resource on drug resistance mutations inM. tuberculosis.

Unique Transcriptome Signature of Mycobacterium tuberculosis in Pulmonary Tuberculosis

ABSTRACT Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identification of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal information from our DNA array analyses, we analyzed the differentially expressed genes within the context of computationally inferred protein networks. Protein networks were constructed using functional linkages established by the Rosetta stone, phylogenetic profile, conserved gene neighbor, and operon computational methods. This combined approach revealed that during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of genes involved in active fortification and evasion from host defense systems. These genes may provide targets for novel intervention strategies.

A specific secretion system mediates PPE41 transport in pathogenic mycobacteria.

Mycobacterial genomes contain two unique gene families, the so‐called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT‐6‐like secretion system. This cluster, designated ESX‐5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX‐5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX‐5 mutant of M. marinum was affected in spreading to uninfected macrophages.

Inference of protein function and protein linkages in Mycobacterium tuberculosis based on prokaryotic genome organization: a combined computational approach

The genome of Mycobacterium tuberculosis was analyzed using recently developed computational approaches to infer protein function and protein linkages. We evaluated and employed a method to infer genes likely to belong to the same operon, as judged by the nucleotide distance between genes in the same genomic orientation, and combined this method with those of the Rosetta Stone, Phylogenetic Profile and conserved Gene Neighbor computational methods for the inference of protein function.

The protein network as a tool for finding novel drug targets.

Proteins are often referred to as the molecular workhorses of the cell since they are responsible for the majority of functions within a living cell. From the generation of energy, to the replication of DNA, proteins play a central role in most cellular functions. Because of their importance to cellular viability, proteins are commonly the target of therapeutic drugs, ranging from antimicrobial to anticancer drugs. With the rise of drug resistant and multi-drug resistant forms of many diseases, it has become increasingly important to develop new strategies to identify alternative drug targets. One such strategy arises from the analysis of protein networks. Protein networks help define individual proteins within the context of all other cellular proteins. In this chapter we discuss methods for the identification and analysis of genome-wide protein networks, and discuss how protein networks can be used to aid the identification of novel drug targets.

Structural and Biochemical Features of the Kv1.3 Potassium Channel: An Aid to Guided Drug Design

The Kv1.3 potassium channel in T lymphocytes plays a major role in mitogen-induced activation and is widely recognized as a potential therapeutic target for immunosuppressive agents. Availability of s

Microbiology: Bacterial transmission tactics

Genome sequencing of Mycobacterium abscessus strains that infect the lungs suggests a possible shift in the bacteriums mode of infection from environmental acquisition to human transmission. This finding has clinical implications.

Complete Genome Sequence of Mycobacteriumchimaera Strain CDC2015-22-71

ABSTRACT Mycobacterium chimaera is a nontuberculous mycobacterium species commonly found in the environment. Here, we report the first complete genome sequence of a strain from the investigation of invasive infections following open-heart surgeries that used contaminated LivaNova Sorin Stockert 3T heater-cooler devices.

Mycobacterium talmoniae sp. Nov., a slowly growing mycobacterium isolated from human respiratory samples

A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide identity (ANI) between their genomes was 99.7 % and phylogenetic comparisons classified the novel mycobacteria as the basal most species in the slowly growing Mycobacterium clade. Mycobacterium avium is the most closely related species based on rpoB gene sequence similarity (92 %), but the ANI between the genomes was 81.5 %, below the suggested cut-off for differentiating two species (95 %). Mycolic acid profiles were more similar to M. avium than to Mycobacterium simiae or Mycobacterium abscessus. The phenotypic and genomic data support the conclusion that the two related isolates represent a novel Mycobacterium species for which the name Mycobacterium talmoniae sp. nov. is proposed. The type strain is NE-TNMC-100812T (=ATCC BAA-2683T=DSM 46873T).

Research, Collaboration, and Open Science Using Web 2.0

There is little doubt that the Internet has transformed the world in which we live. Information that was once archived in bricks and mortar libraries is now only a click away, and people across the globe have become connected in a manner inconceivable only 20 years ago. Although many scientists and educators have embraced the Internet as an invaluable tool for research, education and data sharing, some have been somewhat slower to take full advantage of emerging Web 2.0 technologies. Here we discuss the benefits and challenges of integrating Web 2.0 applications into undergraduate research and education programs, based on our experience utilizing these technologies in a summer undergraduate research program in synthetic biology at Harvard University. We discuss the use of applications including wiki-based documentation, digital brainstorming, and open data sharing via the Web, to facilitate the educational aspects and collaborative progress of undergraduate research projects. We hope to inspire others to integrate these technologies into their own coursework or research projects.