Clofazimine, a lipophilic riminophenazine antibiotic, possesses both antimycobacterial and anti-inflammatory activities. However, its efficacy has been demonstrated only in the treatment of leprosy, not in human tuberculosis, despite the fact that this agent is impressively active in vitro against multidrug-resistant strains of Mycobacterium tuberculosis. Recent insights into novel targets and mechanisms of antimicrobial and anti-inflammatory activity coupled with the acquisition of innovative drug delivery technologies have, however, rekindled interest in clofazimine as a potential therapy for multidrug- and extensively multidrug-resistant tuberculosis in particular, as well as several autoimmune diseases. The primary objective of this review is to critically evaluate these recent developments and to assess their potential impact on improving the therapeutic efficacy and versatility of clofazimine.

Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F/F-ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.

These observations demonstrate that the major K+ transporter of MTB, Trk, as well as an uncharacterized inducible back-up system, is equally sensitive to the inhibitory actions of clofazimine.

Facial appearance is thought to indicate immunity in humans, but very few studies have tested this relationship directly. The aim of this study was to test the relationship between direct measures of immunity, perceived facial health and attractiveness, and facial cues in African men. We show that men with a stronger cytokine response are considered significantly more attractive and healthy. Men with more masculine, heavier facial features (i.e. muscular appearance) have a significantly higher cytokine response and appear significantly healthier and more attractive, while men with a yellower, lighter, "carotenoid" skin colour, have a marginally higher immune response and are also considered significantly more healthy and attractive. In contrast, more symmetrical, skinnier looking men appeared more attractive and healthier, but did not have a stronger cytokine response. These findings also shed new light on the "androgen-mediated" traits proposed by the immunocompetence handicap hypothesis (ICHH) and we propose that facial muscularity serves as a better estimate of an "androgenmediated" trait than facial masculinity. Finally, we build on previous evidence to show that men's facial features do indeed reveal aspects of immunity, even better than more traditional measures of health, such as body mass index (BMI).Evolutionary theory propose that healthy individuals provide various benefits to their partners, such as reduced risk of infection, increased resources 1 and 'good genes' , which are passed on to the offspring 2 . The 'good genes' hypothesis states that females choose mates that display traits which indicate high genetic quality, especially in terms of a higher resistance to pathogens 2 . Women are therefore generally expected to choose healthier men 3 , but which traits do they use to assess health and immunity?Facial attractiveness is highly correlated with perceived health 4, 5 and is considered to serve as a trait indicating good health and a strong immune response 6, 7 . Several facial cues are known to influence attractiveness and health, namely: symmetry; averageness (how closely the face resembles the majority of other faces in the population); sexual dimorphism (masculinity/femininity); skin colour and texture; and facial adiposity (or facial fatness). Most of the facial cues, apart from masculinity (e.g. manly traits, such as a prominent brow ridge and wider jaws), are consistently associated with attractiveness and perceived health (for review see refs 8-13). Masculinity and facial adiposity are also generally associated with measures of actual health, while support for averageness and symmetry are weak or inconsistent and colour has barely been evaluated 8,10,[13][14][15] . Interestingly, recent studies indicate that facial adiposity might be a better indicator of health outcomes than traditional measures of obesity, such as the Body Mass Index (BMI), percentage body fat or waist girth 10,16 . Here we focus specifically on the relationship between facial appearance and measures of immune response...