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Despite organisations' efforts to build and maintain mutually beneficial long-term relationships with customers, not all customers want to reciprocate such relationship building efforts with supplier organisations. It is thus essential that organisations focus their relationship marketing efforts on those customers displaying the intention to build relationships. Organisations must also realise the importance of ensuring customer satisfaction, as there is a positive relationship between customer satisfaction and customer loyalty. The purpose of this study was to determine the extent to which SMEs' relationship intentions and customer satisfaction predict their loyalty to a South African risk financier. Results from hierarchical multiple regression indicate that SMEs' relationship intentions and their satisfaction predict their loyalty towards their risk financier. It was also established that SME customers' satisfaction fulfilled a mediating role between their relationship intentions and loyalty towards the risk financier. This study broadens the current understanding of customer loyalty, especially in B2B settings.

This article investigates internal communication at DaimlerChrysler South Africa (DCSA) from a two-way symmetrical model of internal communication and internal marketing perspective. Results show that, for DCSA to improve effective internal communication and corporate efficiency, it needs to adjust its corporate culture and nature of internal communication according to the principles of both two-way symmetrical communication and internal marketing. [PUBLICATION ABSTRACT]

The effect of increasing competition, globalization and tough economic conditions has led to changes in how banking and life insurance firms operate. This has resulted in banking and life insurance firms focusing on retaining and building long-term relationships with their existing customer base by implementing a relationship marketing strategy. However, not all customers are willing to invest in building long-term relationships. Therefore, firms need to identify and target those customers who intend to support long-term relationships with the firm, that is those with a high relationship intention. The objective of this research was to investigate South African banking and life insurance customers’ relationship intention by determining the constructs constituting relationship intention and to determine whether differences exist between high and low-relationship intention customers for the identified relationship intention constructs. A non-probability, convenience sample was used to gather data from 401 respondents, with 202 from banking and 199 from life insurance customers. The results identified five constructs constituting relationship intention for the sample of respondents and indicated that high- and low-relationship intention respondents see four of the five constructs differently.

South African airline passengers' relationship length with airlines as well as their satisfaction with airlines' service recovery efforts was used to determine the effect of a service failure on their relationship with airlines as well as their willingness to recommend airlines to others following a service failure. The results are compared with the findings from a similar study among United States airline passengers. The comparison reveals while relationship length influence the effect of service failures on U.S. passengers' relationship with and their willingness to recommend an airline, South African passengers are more influenced by their satisfaction with airlines' service recovery efforts. [PUBLICATION ABSTRACT]

The metabolic events associated with maintaining redox homeostasis in Mycobacterium tuberculosis (Mtb) during infection are poorly understood. Here, we discovered a novel redox switching mechanism by which Mtb WhiB3 under defined oxidizing and reducing conditions differentially modulates the assimilation of propionate into the complex virulence polyketides polyacyltrehaloses (PAT), sulfolipids (SL-1), phthiocerol dimycocerosates (PDIM), and the storage lipid triacylglycerol (TAG) that is under control of the DosR/S/T dormancy system. We developed an in vivo radio-labeling technique and demonstrated for the first time the lipid profile changes of Mtb residing in macrophages, and identified WhiB3 as a physiological regulator of virulence lipid anabolism. Importantly, MtbDeltawhiB3 shows enhanced growth on medium containing toxic levels of propionate, thereby implicating WhiB3 in detoxifying excess propionate. Strikingly, the accumulation of reducing equivalents in MtbDeltawhiB3 isolated from macrophages suggests that WhiB3 maintains intracellular redox homeostasis upon infection, and that intrabacterial lipid anabolism functions as a reductant sink. MtbDeltawhiB3 infected macrophages produce higher levels of pro- and anti-inflammatory cytokines, indicating that WhiB3-mediated regulation of lipids is required for controlling the innate immune response. Lastly, WhiB3 binds to pks2 and pks3 promoter DNA independent of the presence or redox state of its [4Fe-4S] cluster. Interestingly, reduction of the apo-WhiB3 Cys thiols abolished DNA binding, whereas oxidation stimulated DNA binding. These results confirmed that WhiB3 DNA binding is reversibly regulated by a thiol-disulfide redox switch. These results introduce a new paradigmatic mechanism that describes how WhiB3 facilitates metabolic switching to fatty acids by regulating Mtb lipid anabolism in response to oxido-reductive stress associated with infection, for maintaining redox balance. The link between the WhiB3 virulence pathway and DosR/S/T signaling pathway conceptually advances our understanding of the metabolic adaptation and redox-based signaling events exploited by Mtb to maintain long-term persistence.

The current study reveals that in chronic TB, the B cell-deficient μMT strain, relative to wild-type (WT) C57BL/6 mice, displays in the lungs lower levels of inflammation that are associated with decreased CD4 + T cell proliferation, diminished Th1 response, and enhanced levels of interleukin (IL)-10. The latter result raises the possibility that B cells may restrict lung expression of IL-10 in chronic TB. These observations are recapitulated in WT mice depleted for B cells using anti-CD20 antibodies. IL-10 receptor (IL-10R) blockade reverses the phenotypes of decreased inflammation and attenuated CD4 + T cell responses in B cell-depleted mice. Together, these results suggest that in chronic murine TB, B cells, by virtue of their capacity to restrict expression of the anti-inflammatory and immunosuppressive IL-10 in the lungs, promote the development of a robust protective Th1 response, thereby optimizing anti-TB immunity. This vigorous Th1 immunity and restricted IL-10 expression may, however, allow the development of inflammation to a level that can be detrimental to the host. Indeed, decreased lung inflammation observed in chronically infected B cell-deficient mice, which exhibit augmented lung IL-10 levels, is associated with a survival advantage relative to WT animals. Collectively, the results reveal that in chronic murine TB, B cells play a role in modulating the protective Th1 immunity and the anti-inflammatory IL-10 response, which results in augmentation of lung inflammation that can be host-detrimental. Intriguingly, in tuberculous human lungs, conspicuous B cell aggregates are present in close proximity to tissue-damaging lesions manifesting necrosis and cavitation, suggesting the possibility that in human TB, B cells may contribute to the development of exacerbated pathology that is known to promote transmission. Since transmission is a major hindrance to TB control, investigating into whether B cells can shape the development of severe pulmonic pathological responses in tuberculous individuals is warranted.

In order to sustain a persistent infection, Mycobacterium tuberculosis ( Mtb ) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc 1 /aa 3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, the presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the cytochrome bd oxidase is specifically required for resisting the adaptive immune response. While the bd oxidase was dispensable for growth in resting macrophages and the establishment of infection in mice, this complex was necessary for optimal fitness after the initiation of adaptive immunity. This requirement was dependent on lymphocyte-derived interferon gamma (IFNγ), but did not involve nitrogen and oxygen radicals that are known to inhibit respiration in other contexts. Instead, we found that ΔcydA mutants were hypersusceptible to the low pH encountered in IFNγ-activated macrophages. Unlike wild type Mtb , cytochrome bd -deficient bacteria were unable to sustain a maximal oxygen consumption rate (OCR) at low pH, indicating that the remaining cytochrome bc 1 /aa 3 complex is preferentially inhibited under acidic conditions. Consistent with this model, the potency of the cytochrome bc 1 /aa 3 inhibitor, Q203, is dramatically enhanced at low pH. This work identifies a critical interaction between host immunity and pathogen respiration that influences both the progression of the infection and the efficacy of potential new TB drugs.

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1+ PD-L1+ myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.MIBI-TOF is a mass spectrometry-based multiplexed imaging platform that has been used to map tumors. In this Resource article, MIBI-TOF is used to provide a spatial atlas of immune responses within human tuberculosis granulomas.

The approval of bedaquiline (BDQ) for the treatment of tuberculosis has generated substantial interest in inhibiting energy metabolism as a therapeutic paradigm. However, it is not known precisely how BDQ triggers cell death in Mycobacterium tuberculosis ( Mtb) . Using 13 C isotopomer analysis, we show that BDQ-treated Mtb redirects central carbon metabolism to induce a metabolically vulnerable state susceptible to genetic disruption of glycolysis and gluconeogenesis. Metabolic flux profiles indicate that BDQ-treated Mtb is dependent on glycolysis for ATP production, operates a bifurcated TCA cycle by increasing flux through the glyoxylate shunt, and requires enzymes of the anaplerotic node and methylcitrate cycle. Targeting oxidative phosphorylation (OXPHOS) with BDQ and simultaneously inhibiting substrate level phosphorylation via genetic disruption of glycolysis leads to rapid sterilization. Our findings provide insight into the metabolic mechanism of BDQ-induced cell death and establish a paradigm for the development of combination therapies that target OXPHOS and glycolysis. Bedaquiline (BDQ) is a known tuberculosis treatment, but the precise mechanism of cell death is unclear. Here, the authors explore the metabolic profiles of M. tuberculosis upon BDQ treatment and find reliance on glycolysis and synergistic cell death when oxidative phosphorylation is also targeted.

Hydrogen sulfide (H 2 S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and • NO. However, the importance of host-derived H 2 S in microbial pathogenesis is unknown. Here we show that Mtb -infected mice deficient in the H 2 S-producing enzyme cystathionine β-synthase (CBS) survive longer with reduced organ burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. High-resolution respirometry, transcriptomics and mass spectrometry establish that H 2 S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H 2 S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H 2 S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H 2 S to promote growth and disease, and suggest that host-directed therapies targeting H 2 S production may be potentially useful for the management of tuberculosis and other microbial infections. The importance of host-produced hydrogen sulfide (H 2 S) in microbial pathogenesis is poorly understood. Here, Saini et al. show that H 2 S alters Mycobacterium tuberculosis (Mtb) central metabolism, stimulates respiration to promote growth and TB disease, and upregulates the Dos regulon.