Strange particles observed by an experiment in Antarctica could be evidence of an alternative reality where everything is upside down

Temperature checks, compulsory face masks and scrupulous hygiene - it's more like going to a hospital than a school, but the Shanghai students returning to class after three months of lockdown are...

As Thailand's capital cautiously reopens many restaurants shuttered over coronavirus fears, the feline "employees" of the Caturday Cafe are back at work.

Across Africa, centuries-old cultural traditions are being foregone in the wake of the COVID-19 pandemic, which has seen governments impose restrictions on gatherings and other practices around death and burial. Francesca Lynagh reports.

Artist Ken Rinaldo encourages the bacteria on banknotes to grow and spread to explore colonialism in his touring show, Borderless Bacteria/Colonialist Cash

Silver has an antibacterial effect by stopping the motors that bacteria use to move around from working properly and making them move more slowly

Some bacteria sacrifice themselves when their colony is attacked by rivals, to save their relatives and make sure their shared genes are passed on

Soil’s earthy smell comes from chemicals produced by bacteria called Streptomyces, which use the odour to attract springtails to help disperse their spores

The Atacama Desert is one of the most hostile places on Earth, but new microbes arrive there every day on dust grains carried by the wind

Buildings may one day be made using a strain of bacteria that creates a concrete-like material when combined with sand and nutrients

Efforts to prevent prisoners from reoffending are often lacking in scientific rigour and can even fly in the face of available evidence

Your immune system ages too, weakening as you get older and making you more susceptible to infections. Fortunately, we are discovering plenty of things you can do to turn back the clock and stay healthy

Romans flocked to the city's bars and cafes for their caffeine fix on Tuesday - but only takeaway options are permitted.

Antwerp is regaining its glitz as Belgium eases a two-month nationwide coronavirus lockdown that virtually halted business in the world's largest diamond trade centre.

A Backstage Pass with Christopher Dragon: Creating that HARMAN Experience at the World's Largest Technology Show Around the world, many companies are preparing to close out the year, but for HARMAN, it’s time to head to Las Vegas once again for the...

Your immune system ages too, weakening as you get older and making you more susceptible to infections. Fortunately, we are discovering plenty of things you can do to turn back the clock and stay healthy

Strange particles observed by an experiment in Antarctica could be evidence of an alternative reality where everything is upside down

With major sports leagues preparing for the eventuality of restarting behind closed doors amid the coronavirus pandemic, NBA commissioner Adam Silver reportedly took the concept to the next level on Friday.

Taiwan reopened baseball games to a limited number of fans on Friday for the first time since controls were imposed to limit the spread of the coronavirus, part of government efforts to slowly allow normal life to resume.

With major sports leagues preparing for the eventuality of restarting behind closed doors amid the coronavirus pandemic, NBA commissioner Adam Silver reportedly took the concept to the next level on Friday.

Expensive, risky and involving scores of people, live theater may be the last form of entertainment to come back - and will likely look very different when the curtain raises.

Across Africa, centuries-old cultural traditions are being foregone in the wake of the COVID-19 pandemic, which has seen governments impose restrictions on gatherings and other practices around death and burial. Francesca Lynagh reports.

Some dogs and cats may be passing gut microbes to their owners that withstand last-resort antibiotics, which can be needed to fight off pneumonia from a coronavirus infection

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Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (_CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of _CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.

ABSTRACT

Synthesis and cleavage of the cell wall polymer peptidoglycan (PG) are carefully orchestrated processes and are essential for the growth and survival of bacteria. Yet, the function and importance of many enzymes that act on PG in Mycobacterium tuberculosis remain to be elucidated. We demonstrate that the activity of the N-acetylmuramyl-l-alanine amidase Ami1 is dispensable for cell division in M. tuberculosis in vitro yet contributes to the bacterium’s ability to persist during chronic infection in mice. Furthermore, the d,l-endopeptidase RipA, a predicted essential enzyme, is dispensable for the viability of M. tuberculosis but required for efficient cell division in vitro and in vivo. Depletion of RipA sensitizes M. tuberculosis to rifampin and to cell envelope-targeting antibiotics. Ami1 helps sustain residual cell division in cells lacking RipA, but the partial redundancy provided by Ami1 is not sufficient during infection, as depletion of RipA prevents M. tuberculosis from replicating in macrophages and leads to dramatic killing of the bacteria in mice. Notably, RipA is essential for persistence of M. tuberculosis in mice, suggesting that cell division is required during chronic mouse infection. Despite the multiplicity of enzymes acting on PG with redundant functions, we have identified two PG hydrolases that are important for M. tuberculosis to replicate and persist in the host.

IMPORTANCE Tuberculosis (TB) is a major global heath burden, with 1.6 million people succumbing to the disease every year. The search for new drugs to improve the current chemotherapeutic regimen is crucial to reducing this global health burden. The cell wall polymer peptidoglycan (PG) has emerged as a very successful drug target in bacterial pathogens, as many currently used antibiotics target the synthesis of this macromolecule. However, the multitude of genes encoding PG-synthesizing and PG-modifying enzymes with apparent redundant functions has hindered the identification of novel drug targets in PG synthesis in Mycobacterium tuberculosis. Here, we demonstrate that two PG-cleaving enzymes are important for virulence of M. tuberculosis. In particular, the d,l-endopeptidase RipA represents a potentially attractive drug target, as its depletion results in the clearance of M. tuberculosis from the host and renders the bacteria hypersusceptible to rifampin, a frontline TB drug, and to several cell wall-targeting antibiotics.

ABSTRACT

The synergy between Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by which M. tuberculosis exacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with M. tuberculosis, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically, M. tuberculosis-specific exosomes realigned mitochondrial and nonmitochondrial oxygen consumption rates (OCR) and modulated the expression of host genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics analyses revealed the enrichment of several host factors (e.g., HIF-1α, galectins, and Hsp90) known to promote HIV-1 reactivation in M. tuberculosis-specific exosomes. Treatment with a known antioxidant—N-acetyl cysteine (NAC)—or with inhibitors of host factors—galectins and Hsp90—attenuated HIV-1 reactivation by M. tuberculosis-specific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-M. tuberculosis coinfection, which will enable the design of effective therapeutic strategies.

IMPORTANCE Globally, individuals coinfected with the AIDS virus (HIV-1) and with M. tuberculosis (causative agent of tuberculosis [TB]) pose major obstacles in the clinical management of both diseases. At the heart of this issue is the apparent synergy between the two human pathogens. On the one hand, mechanisms induced by HIV-1 for reactivation of TB in AIDS patients are well characterized. On the other hand, while clinical findings clearly identified TB as a risk factor for HIV-1 reactivation and associated mortality, basic mechanisms by which M. tuberculosis exacerbates HIV-1 replication and infection remain poorly characterized. The significance of our research is in identifying the role of fundamental mechanisms such as redox and energy metabolism in catalyzing HIV-M. tuberculosis synergy. The quantification of redox and respiratory parameters affected by M. tuberculosis in stimulating HIV-1 will greatly enhance our understanding of HIV-M. tuberculosis coinfection, leading to a wider impact on the biomedical research community and creating new translational opportunities.