Plants on the planet live in a microbe-rich ecosystem, interacting with different microbes, including pathogenic, beneficial, and other commensal microbes with unknown functions, which results in diverse impacts on plants. Pathogen infections have negative effects on plants, which cause approximately 30% of the crop losses worldwide annually. The global food shortage and food security problems become more severe with the growing population at a time with increased climate change. Thus, it is extremely important to control destructive diseases and develop efficient strategies to enhance plant resistance, such as through the gene manipulation. In addition, beneficial microbes are considered the efficient alternative to the conventional plant protection chemicals, which are vital for sustainable agriculture. I apply the Arabidopsis thaliana and Pseudomonas syringae pathovar tomato (Pto) as the main interaction model to study the molecular and genetic mechanisms of Arabidopsis -Pto interactions. My three main discoveries are reported in Chapters 2, 3 and 4. In addition, in Chapter 5, I summarize how I identified a new Bacillus strain and investigated its modes of action of the related biological control and growth promotion activities on strawberry plants. Plants have evolved constitutive and inducible defenses to combat harmful pathogens. The constitutive defense responses are present in plants before infections, such as the plant physical structures and chemical toxins. The induced defenses rely on two interconnected layers, the pattern triggered immunity (PTI) and effector triggered immunity (ETI). In Chapters 2, 3 and 4, I describe my discovery of three novel components involved in PTI. In Chapter 2, it is known that Acyl Carrier Proteins (ACPs) are the central components for fatty acid biosynthesis. I demonstrate that ACP1, one of the eight Arabidopsis ACPs, limits the magnitude of PTI by influencing fatty acid biosynthesis. Specifically, the reduced levels of linolenic acid (18:3 FA) in the leaves of acp1 mutant plants underlie the enhanced resistance against Pto DC3000 through the effects on the phytohormone jasmonic acid (JA) and salicylic acid (SA) accumulation and the related signaling pathways. Chapter 3 describes that Plasma Membrane (PM) H+-ATPases 5 (AHA5) is negatively involved in PTI by affecting a series of defense responses, including the stomatal movement, callose deposition, defense-related gene expression, and defense hormone SA accumulation for PTI in Arabidopsis. AHA5 physically interacts with a vital defense regulator, RPM1 Interacting Protein 4 (RIN4) in vitro and in vivo, which might also be critical for its function in PTI. Besides, AHA5 may couple the proton (H+) pumping with the H2O2 production during the PTI. In Chapter 4, I discover that AtMIN7, a key component involved in the vesicle trafficking system, is critical for the cuticle formation and related defense against the bacterial pathogen Pto. The atmin7 mutant leaves show a thinner cuticular layer, defective stomata structure, and impaired cuticle ledge of stomata compared to the leaves of wild-type plants via the direct observation by the transmission electron microscopy and scanning electron microscopy. The GC–MS analysis further reveals that the amount of cutin monomers is significantly reduced in atmin7 mutant plants. The transcriptome analysis shows that the genes related to lipid transfer proteins (LTPs), ABC transporters, and cutin biosynthesis are significantly downregulated in atmin7 mutant plants. Thus, the transport of cutin-related components by AtMIN7 may contribute to the cuticle formation and related defense function. In Chapter 5, I identify the Bacillus strain XY22, showing a remarkable biocontrol effect on the strawberry Fusarium wilt disease and displaying efficient plant growth promotion by inducing vegetative growth and increasing fruit yield under greenhouse conditions. Further studies show that XY22 is capable to produce multiple extracellular enzymes and microbial metabolites, which might contribute to the pathogen disease suppression and plant growth promotion. Also, XY22 can induce the plant systemic defense responses during the plant-pathogen interaction. Fusarium wilt of strawberries caused by Fusarium oxysporum f sp Fragariae (Fof) is a destructive disease that constitutes a significant threat to the strawberry industry and has resulted in substantial economic losses throughout the U.S. and worldwide. Our study provides a promising approach to control the related destructive pathogen and disease through a sustainable approach. Taken together, the studies presented in this dissertation enrich our understanding of plant-microbe interactions in different aspects. Discovering novel critical genes/pathways and beneficial microbes involved in plant immunity as well as investigating the mechanisms of the related functional mechanisms will provide us more efficient strategies to enhance plant health and yield for developing the sustainable agriculture with the reduced harmful chemical applications.