Citation: Tsotetsi, T.; Nephali, L.; Malebe, M.; Tugizimana, F. Bacillus for Plant Growth Promotion and Stress Resilience: What Have We Learned? Plants 2022, 11, 2482. https://doi.org/10.3390/ plants11192482 Academic Editor: Barbara Hawrylak-Nowak Received: 3 September 2022 Accepted: 19 September 2022 Published: 22 September 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). plants Review Bacillus for Plant Growth Promotion and Stress Resilience: What Have We Learned? Teboho Tsotetsi 1, *, Lerato Nephali 1 , Motumiseng Malebe 1 and Fidele Tugizimana 1,2, * 1 Department of Biochemistry, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa 2 International R&D Division, Omnia Nutriology, Omnia Group (Pty) Ltd., Johannesburg 2021, South Africa * Correspondence: ttsotetsi@uj.ac.za (T.T.); fidele.tugizimana@omnia.co.za (F.T.); Tel.: +27-11-559-7784 (F.T.); Fax: +27-11-559-2370 (F.T.) Abstract: The rhizosphere is a thin film of soil that surrounds plant roots and the primary location of nutrient uptake, and is where important physiological, chemical, and biological activities are occurring. Many microbes invade the rhizosphere and have the capacity to promote plant growth and health. Bacillus spp. is the most prominent plant growth promoting rhizobacteria due to its ability to form long-lived, stress-tolerant spores. Bacillus-plant interactions are driven by chemical languages constructed by a wide spectrum of metabolites and lead to enhanced plant growth and defenses. Thus, this review is a synthesis and a critical assessment of the current literature on the application of Bacillus spp. in agriculture, highlighting gaps that remain to be explored to improve and expand on the Bacillus-based biostimulants. Furthermore, we suggest that omics sciences, with a focus on metabolomics, offer unique opportunities to illuminate the chemical intercommunications between Bacillus and plants, to elucidate biochemical and molecular details on modes of action of Bacillus-based formulations, to generate more actionable insights on cellular and molecular events that explain the Bacillus-induced growth promotion and stress resilience in plants. Keywords: Bacillus; biostimulant; plant growth; stress resilience; metabolomics 1. Introduction Edaphic factors and genetics play a pivotal role in the growth and yield of crop plants [1]. Over the past decades, genetic engineering and plant breeding approaches have been employed to develop new cultivars with desired traits, such as high yield and resistance to environmental stresses [2]. However, there is a less commercial success for genetically modified crops due to ethical constraints concerning genetically modified organisms (GMO) [3]. To obtain better crop yield, applications of chemical fertilizers have been the opted strategy. However, over time, studies and empirical evidence have shown that this traditional method—the use of chemical fertilizers—is not sustainable due to the inherent negative effects these products have on the environment. The excessive utilization of chemical fertilizers has shown to lead to toxic build-up of heavy metals, soil acidification and soil crust, thereby reducing the soil content of organic matter and humic substance. Soil acidification reduces crop phosphate intake, raises the concentration of harmful ions in the soil, and inhibits crop growth [4]. The incorporation of biostimulants, such as plant growth-promoting rhizobacteria (PGPR)-based formulations, in cropping systems has increasingly shown to be a promising strategy for sustainable agriculture and global food security, aligning with the United Nations sustainable development goals (SDGs) [5]. A broad array of bacterial species has been reported to possess plant growth-promoting attributes with the prominent species be- longing to the genus Bacillus. Members of the genus Bacillus are ubiquitous, Gram-positive, and aerobic bacteria [6,7]. Bacillus species produce a multitude of enzymes, antibiotics, and metabolites which give them prominent applications in various sectors such as pharmaceu- ticals and agriculture. Furthermore, their uniqueness and popularity arise from their spore Plants 2022, 11, 2482. https://doi.org/10.3390/plants11192482 https://www.mdpi.com/journal/plants