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Pseudomonas syringae is a Gram-negative and model pathogenic bacterium that causes plant diseases worldwide. Here, we set out to identify binding motifs for all 301 annotated transcription factors (TFs) of P. syringae using HT-SELEX. We successfully identify binding motifs for 100 TFs. We map functional interactions between the TFs and their targets in virulence-associated pathways, and validate many of these interactions and functions using additional methods such as ChIP-seq, electrophoretic mobility shift assay (EMSA), RT-qPCR, and reporter assays. Our work identifies 25 virulence-associated master regulators, 14 of which had not been characterized as TFs before. The authors set out to identify binding motifs for all 301 transcription factors of a plant pathogenic bacterium, Pseudomonas syringae , using HT-SELEX. They successfully identify binding motifs for 100 transcription factors, infer their binding sites on the genome, and validate the predicted interactions and functions.

Bacteria have developed a large array of motility mechanisms to exploit available resources and environments. These mechanisms can be broadly classified into swimming in aqueous media and movement over solid surfaces. Swimming motility involves either the rotation of rigid helical filaments through the external medium or gyration of the cell body in response to the rotation of internal filaments. On surfaces, bacteria swarm collectively in a thin layer of fluid powered by the rotation of rigid helical filaments, they twitch by assembling and disassembling type IV pili, they glide by driving adhesins along tracks fixed to the cell surface and, finally, non-motile cells slide over surfaces in response to outward forces due to colony growth. Recent technological advances, especially in cryo-electron microscopy, have greatly improved our knowledge of the molecular machinery that powers the various forms of bacterial motility. In this Review, we describe the current understanding of the physical and molecular mechanisms that allow bacteria to move around.In this Review, Wadhwa and Berg explore the most common bacterial motility mechanisms and summarize the current understanding of the molecular machines that enable bacteria to swim in aqueous media and move on solid surfaces.

Osteomyelitis remains one of the greatest risks in orthopaedic surgery. Although many organisms are linked to skeletal infections, Staphylococcus aureus remains the most prevalent and devastating causative pathogen. Important discoveries have uncovered novel mechanisms of S. aureus pathogenesis and persistence within bone tissue, including implant-associated biofilms, abscesses and invasion of the osteocyte lacuno-canalicular network. However, little clinical progress has been made in the prevention and eradication of skeletal infection as treatment algorithms and outcomes have only incrementally changed over the past half century. In this Review, we discuss the mechanisms of persistence and immune evasion in S. aureus infection of the skeletal system as well as features of other osteomyelitis-causing pathogens in implant-associated and native bone infections. We also describe how the host fails to eradicate bacterial bone infections, and how this new information may lead to the development of novel interventions. Finally, we discuss the clinical management of skeletal infection, including osteomyelitis classification and strategies to treat skeletal infections with emerging technologies that could translate to the clinic in the future.Osteomyelitis is an infection of bone that arises when a pathogen colonizes bone tissue owing to injury or surgery. In this Review, Masters and colleagues explore the microbial pathogenesis, immunity and clinical management of bone infections.

Iron is an essential trace element for most organisms. A common way for bacteria to acquire this nutrient is through the secretion of siderophores, which are secondary metabolites that scavenge iron from environmental stocks and deliver it to cells via specific receptors. While there has been tremendous interest in understanding the molecular basis of siderophore synthesis, uptake and regulation, questions about the ecological and evolutionary consequences of siderophore secretion have only recently received increasing attention. In this Review, we outline how eco-evolutionary questions can complement the mechanistic perspective and help to obtain a more integrated view of siderophores. In particular, we explain how secreted diffusible siderophores can affect other community members, leading to cooperative, exploitative and competitive interactions between individuals. These social interactions in turn can spur co-evolutionary arms races between strains and species, lead to ecological dependencies between them and potentially contribute to the formation of stable communities. In brief, this Review shows that siderophores are much more than just iron carriers: they are important mediators of interactions between members of microbial assemblies and the eukaryotic hosts they inhabit.Secreted siderophores help bacteria to take up iron from the environment. In this Review, Kramer, Özkaya and Kümmerli discuss the functions and implications that siderophores have for social interactions between bacterial cells and the resulting consequences for communities and hosts.

The dynamic and polymicrobial oral microbiome is a direct precursor of diseases such as dental caries and periodontitis, two of the most prevalent microbially induced disorders worldwide. Distinct microenvironments at oral barriers harbour unique microbial communities, which are regulated through sophisticated signalling systems and by host and environmental factors. The collective function of microbial communities is a major driver of homeostasis or dysbiosis and ultimately health or disease. Despite different aetiologies, periodontitis and caries are each driven by a feedforward loop between the microbiota and host factors (inflammation and dietary sugars, respectively) that favours the emergence and persistence of dysbiosis. In this Review, we discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis that have both enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches for oral diseases.

Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies.

In this Review, Brennan and Garrett discuss the multifaceted associations of Fusobacterium nucleatum with its human host that range from symbiotic in oral biofilms to potential infectious pathogen at several sites and cancer-promoting member of the microbiota in the gut.

Antibiotics have transformed medicine, saving millions of lives since they were first used to treat a bacterial infection. However, antibiotics administered to target a specific pathogen can also cause collateral damage to the patient’s resident microbial population. These drugs can suppress the growth of commensal species which provide protection against colonization by foreign pathogens, leading to an increased risk of subsequent infection. At the same time, a patient’s microbiota can harbour potential pathogens and, hence, be a source of infection. Antibiotic-induced selection pressure can cause overgrowth of resistant pathogens pre-existing in the patient’s microbiota, leading to hard-to-treat superinfections. In this Review, we explore our current understanding of how antibiotic therapy can facilitate subsequent infections due to both loss of colonization resistance and overgrowth of resistant microorganisms, and how these processes are often interlinked. We discuss both well-known and currently overlooked examples of antibiotic-associated infections at various body sites from various pathogens. Finally, we describe ongoing and new strategies to overcome the collateral damage caused by antibiotics and to limit the risk of antibiotic-associated infections.In this Review, de Nies, Kobras and Stracy examine the detrimental effects of antibiotics on the microbiota and the resulting associated infections. They delve into the interplay between antibiotic therapy, loss of colonization resistance, overgrowth of resistant bacteria and subsequent infections. They also discuss strategies to mitigate these risks and reduce antibiotic-associated infections.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1–8) vs. 1 (1–3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22–5.83) for COVID-19, and 3.09-fold (1.11–7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.

Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.