The activity of hyaD contributed to the virulence of avian Pasteurella multocida.

Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Antimicrobial susceptibility of Pasteurella multocida strains isolated from different host species.

The spread of antibiotic resistance is one of the biggest challenges of our time, making it difficult to treat bacterial diseases. Pasteurella multocida is a widespread facultative pathogenic bacterium, which causes a wide range of diseases in both mammals and birds. In the present study, antibiotic susceptibility of 155 P. multocida strains were tested using the broth microdilution method to obtain the minimum inhibitory concentration (MIC) values for 15 antibiotics. The most effective antibiotics against pasteurellosis were ceftiofur, tetracycline, doxycycline, florfenicol and tilmicosin. Of the strains, 12 proved to be multi-drug resistant (MDR). To combat antibiotic resistance, it is important to establish a pre-treatment antibiotic susceptibility profile. A well-chosen antibiotic would not only make the treatment more successful but may also slow down the spread of resistance and the evolution of MDR strains.

Developing a PmSLP3-based vaccine formulation that provides robust long-lasting protection against hemorrhagic septicemia-causing serogroup B and E strains of Pasteurella multocida in cattle.

Background: Pasteurella multocida is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic septicemia. Outbreaks of hemorrhagic septicemia in cattle and buffaloes are marked by rapid progression and high mortality. These infections have particularly harmful socio-economic impacts on small holder farmers in Africa and Asia who are heavily reliant on a small number of animals kept as a means of subsistence for milk and draft power purposes. A novel vaccine target, PmSLP-3, has been identified on the surface of hemorrhagic septicemia-associated strains of P. multocida and was previously shown to elicit robust protection in cattle against lethal challenge with a serogroup B strain. Methods: Here, we further investigate the protective efficacy of this surface lipoprotein, including evaluating the immunogenicity and protection upon formulation with a variety of adjuvants in both mice and cattle. Results: PmSLP-3 formulated with Montanide ISA 61 elicited the highest level of serum and mucosal IgG, elicited long-lasting serum antibodies, and was fully protective against serogroup B challenge. Studies were then performed to identify the minimum number of doses required and the needed protein quantity to maintain protection. Duration studies were performed in cattle, demonstrating sustained serum IgG titres for 3 years after two doses of vaccine and full protection against lethal serogroup B challenge at 7 months after a single vaccine dose. Finally, a serogroup E challenge study was performed, demonstrating that PmSLP-3 vaccine can provide protection against challenge by the two serogroups responsible for hemorrhagic septicemia. Conclusion: Together, these data indicate that PmSLP-3 formulated with Montanide ISA 61 is an immunogenic and protective vaccine against hemorrhagic septicemia-causing P. multocida strains in cattle.

Successful Management of Pasteurella multocida Pneumonia in a Chronic Obstructive Pulmonary Disease Patient: A Case Report Highlighting the Importance of Tailored Antibiotic Therapy.

This report describes a patient with Pasteurella multocida pneumonia. The patient was a man in his 70s with significant comorbid conditions, including chronic obstructive pulmonary disease (COPD), and is an example of the diverse presentations of P. multocida infections increasingly found in the literature. The novelty of this case lies in the manifestation of P. multocida pneumonia in a patient with underlying respiratory conditions and its successful management, outlining a unique clinical scenario and a tailored therapeutic approach. A 71-year-old male with a medical history of COPD, asthma, tremors, hypertension, and arthritis presented to the emergency department with progressive shortness of breath, productive cough, and chest tightness. The initial diagnosis was COPD exacerbation and left lower lobe pneumonia, for which a regimen of ceftriaxone and azithromycin was initiated. The patient's condition was further complicated by the persistence of symptoms. Following sputum culture analysis, P. multocida infection was identified. Consequently, the antibiotic regimen was tailored, transitioning the patient to doxycycline, which led to substantial clinical improvement, enabling discharge with a 10-day course of oral doxycycline. This case elucidates the importance of precise microbiological diagnosis in patients with complex respiratory conditions, as it guides more targeted antibiotic therapy. It highlights the need for clinical vigilance for atypical pathogens like P. multocida in patients with COPD exacerbations, especially when conventional treatment strategies yield suboptimal responses. The successful resolution of the pneumonia underscores the effectiveness of antibiotic stewardship guided by sputum culture findings.

Characterisation of Pasteurella multocida Strains from Different Lesions in Rabbits.

Pasteurellosis, a disease caused by Pasteurella multocida, is responsible for economic losses in rabbit industrial farms due to rhinitis, conjunctivitis, pneumonia, metritis, mastitis, orchitis, subcutaneous abscesses, otitis, encephalitis, and septicaemic forms. Although the occurrence of the disease is conditioned by predisposing factors that affect the rabbit immune response, the strains of P. multocida involved in the infection may have a different pathogenic ability. Therefore, typing of strains spread among the rabbits is important to assess their pathogenic potential. The aim of this study is to investigate the P. multocida strains responsible for disease in rabbit industrial farms. A total of 114 strains identified from different lesions were serotyped. Additionally, the presence of virulence-associated genes was investigated using three PCR (polymerase chain reaction) protocols. Capsular type A was prevalently found in strains from respiratory lesions while types D and F in those from metritis, mastitis, and other lesions. Different associations between some virulence-associated genes and both capsular type and lesions found in rabbits were detected. The presence of 8 virulence-associated genes seems to increase the occurrence of metritis. In addition, strains belonging to capsular type A and responsible for respiratory disorders especially, were found equipped with 10 and 11 virulence-associated genes. Nevertheless, the presence of strains responsible only for rhinitis was also detected among the latter, suggesting that the pathogenic ability of the bacteria depends on the expression rather than the presence of a gene.

Septic Arthritis Caused by Pasteurella multocida: A Source Control Issue.

Pasteurella multocida is known to be the most commonly isolated pathogen of soft tissue infections caused by cat or dog-inflicted wounds. We present a case of a 66-year-old female who was bitten by a cat, prescribed antibiotic therapy outpatient, and developed a septic metacarpophalangeal joint despite appropriate antibiotics. A failure to improve with appropriate antibiotic therapy should raise suspicion of a source control problem and prompt surgical intervention, a principle that is highlighted in this case. Pasteurella multocida septic arthritis of the fingers manifests in less than 4% of cases, making this case a rare presentation of a septic joint, which necessitated surgical management.

In field evaluation of impact on clinical signs of an inactivated autogenous vaccine against Pasteurella multocida in rabbits.

In Italy, the use of autogenous inactivated vaccines prepared with the bacterial strains isolated from affected animals is authorized by the Ministry of Health in farms where bacterial diseases occur frequently. The autogenous vaccine performed using Pasteurella multocida is frequently used in rabbit farms, but the feedback of its application is not available. Therefore, the aim of this study is to give information about the impact on the clinical signs of a bivalent autogenous vaccine in rabbits of a genetic centre. The vaccine was prepared using two P. multocida strains belonging to serogroups A and F, equipped with virulence genes and responsible for cyclical outbreak of pasteurellosis in the farm. The vaccine was administered with a first injection, followed by another one after 15 days, then another one four months after the first injection, and then continuing with a further injection every six months to all rabbits. Clinical conditions and mortality rates were monitored for two years after the first vaccination. The improvement in clinical condition and the decrease of the mortality rate were significant especially in the first year post-vaccine. In addition, the number of animals removed due to the disease decreased greatly. Based on the finding of P. multocida strains belonging to serogroup D and serogroup A equipped with different virulence-gene patterns from those previously found, we suggest that the vaccine was unable to prevent the introduction and spreading of new strains among the rabbits.

Role of biofilms in antimicrobial resistance of the bacterial bovine respiratory disease complex.

An increase in chronic, non-responsive bovine respiratory disease (BRD) infections in North American feedlot cattle is observed each fall, a time when cattle are administered multiple antimicrobial treatments for BRD. A number of factors are responsible for BRD antimicrobial treatment failure, with formation of biofilms possibly being one. It is widely accepted that biofilms play a role in chronic infections in humans and it has been hypothesized that they are the default lifestyle of most bacteria. However, research on bacterial biofilms associated with livestock is scarce and significant knowledge gaps exist in our understanding of their role in AMR of the bacterial BRD complex. The four main bacterial species of the BRD complex, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis are able to form biofilms in vitro and there is evidence that at least H. somni retains this ability in vivo. However, there is a need to elucidate whether their biofilm-forming ability contributes to pathogenicity and antimicrobial treatment failure of BRD. Overall, a better understanding of the possible role of BRD bacterial biofilms in clinical disease and AMR could assist in the prevention and management of respiratory infections in feedlot cattle. We review and discuss the current knowledge of BRD bacteria biofilm biology, study methodologies, and their possible relationship to AMR.

Pathogenicity and Genomic Characteristics Analysis of Pasteurella multocida Serotype A Isolated from Argali Hybrid Sheep.

Respiratory diseases arising from co-infections involving Pasteurella multocida (P. multocida) and Mycoplasma ovipneumoniae (Mo) pose a substantial threat to the sheep industry. This study focuses on the isolation and identification of the P. multocida strain extracted from the lung tissue of an argali hybrid sheep infected with Mo. Kunming mice were used as a model to assess the pathogenicity of P. multocida. Subsequently, whole genome sequencing (WGS) of P. multocida was conducted using the Illumina NovaSeq PE150 platform. The whole genome sequencing analysis involved the construction of an evolutionary tree to depict conserved genes and the generation of a genome circle diagram. P. multocida, identified as serotype A, was named P. multocida SHZ01. Our findings reveal that P. multocida SHZ01 infection induces pathological manifestations, including hemorrhage and edema, in mice. The phylogenetic tree of conserved genes analyzing P. multocida from different countries and different host sources indicates close relatedness between the P. multocida SHZ01 strain and the P. multocida 40540 strain (A:12), originating from turkeys in Denmark. The genome of P. multocida SHZ01 comprises 2,378,508 base pairs (bp) with a GC content of 40.89%. Notably, this strain, designated P. multocida, exhibits two distinct gene islands and harbors a total of 80 effector proteins associated with the Type III Secretion System (T3SS). The P. multocida SHZ01 strain harbors 82 virulence genes and 54 resistance genes. In the P. multocida SHZ01 strain, the proteins, genes, and related GO and KEGG pathways have been annotated. Exploring the relationship between these annotations and the pathogenicity of the P. multocida SHZ01 strain would be valuable. This study holds great significance in further understanding the pathogenesis and genetic characteristics of the sheep-derived P. multocida SHZ01 strain. Additionally, it contributes to our understanding of respiratory diseases in the context of co-infection.

Gamma Irradiated Pasteurella multocida Vaccine induces strong humoral immunity and protects rabbits from disease.

Pasteurella multocida is affecting a multitude of animals and severely affects livestock production. Existing vaccines are mostly chemically inactivated and do not lead to wide protection. Irradiated vaccines are enjoying a renaissance and the concept of "replication defficient but metabolically active" vaccines was recently evaluated in several vaccine trials. P. multocida was isolated from the nasal swab, blood, and lung swab samples from infected rabbits. Gamma irradiation of P. multocida for inhibition of replication was evaluated at an optimized irradiation dose of 10 Kgy established. Four groups of rabbits were (mock) vaccinated with a commercial P. multocida vaccine and three irradiated formulations as liquid, lyophilized formulations with added Trehalose and lyophilized-Trehalose with an "activation" culturing the irradiated bacteria for 24 in broth. Evaluation of humoral immune response by ELISA showed that all three irradiated vaccines produced an effective, protective, and continued IgG serum level after vaccination and bacterial challenge. The IFN-γ expression is maintained at a normal level, within each individual group however, the lyophilized trehalose irradiated vaccine showed peak mean of IFN-γ titer at one week after booster dose (day 21) which was statistically significant. Cumulatively, the results of this study show that gamma-irradiated P. multocida vaccines are safe and protect rabbits against disease. Moreover, Rabbits' immunization with the three irradiated formulations avoided adverse side effects as compared to commercial polyvalent vaccine, the body weight gain for the irradiated vaccine groups indicates less stress compared to the commercial polyvalent vaccine.

Two cases of respiratory infection due to Pasteurella multocida: Acute and chronic form.

We present two cases of Pasteurella multocida (P. multocida) respiratory infection. The first case involves a 62-year-old female with abnormal chest shadows, a history of bronchial asthma, and colorectal cancer. Endobronchial ultrasound with a guide sheath (EBUS-GS) revealed granulomatous changes, and P. multocida was cultured. The second case is a 64-year-old female presenting to the emergency department with progressively worsening chest pain and dyspnea, with P. multocida detected from her sputum culture. Treatment with penicillin antibiotics resulted in symptom improvement and normalization of CT findings. These cases indicate the importance of considering P. multocida in respiratory infections, given the patients' history of pet ownership and the nonspecific imaging findings and symptoms. This highlights the necessity for accurate diagnosis and appropriate antibiotic treatment, particularly in cases where animal traumatic exposure is not detected.

Dogs Licks Are Not Benign: Pasturella Multocida Bacteremia From Household Dog.

Pasturella (P.) multocida is a gram-negative coccobacilli commonly colonized in the oral, nasopharyngeal, and upper respiratory tracts of animals. Infections due to P. multocida range in severity, and symptoms largely depend on underlying immune status and co-morbid conditions. Widely known, the transmission of P. multocida is commonly thought to occur through biting and skin breakage alone. However, multiple studies have highlighted instances of severe complications secondary to transmission through the passage of P. multocida through animal licking alone without skin disruption. Here, we present a case of a nonagenarian female presenting with septic shock secondary to P. multocida with the source of transmission found to be secondary to the patient's dog licking her chronic leg wounds. We also highlight other instances of similar transmission through a literature review, including common treatment courses. We aim to raise awareness of common transmissions of bacteria, specifically P. multocida, along with broadening differentials when one presents with skin and soft tissue infections.

Antimicrobial Susceptibility Profiles of Pasteurella multocida Isolates from Clinical Cases of Waterfowl in Hungary between 2022 and 2023.

The waterfowl industry represents a narrow, yet economically significant, sector within the poultry industry. Although less prominent, the waterfowl sector is nonetheless of equal importance to any other livestock sector in terms of antimicrobial resistance and animal health issues. This study assesses the antimicrobial resistance profile of Pasteurella multocida bacterial strains isolated from clinical cases in Hungary's duck and goose populations, determining the minimal inhibitory concentration (MIC) of 27 samples collected from 15 different locations. The results indicate that the isolated strains were susceptible to most antibiotics, except for notable resistance to enrofloxacin. These findings support that Pasteurella multocida largely retained its susceptibility. However, the observed resistance to enrofloxacin suggests overuse of fluoroquinolones, which indicates the potential need for stricter regulation of their use in the poultry industry.

Comparative Minimum Inhibitory and Mutant Prevention Drug Concentrations for Pradofloxacin and Seven Other Antimicrobial Agents Tested against Bovine Isolates of Mannheimia haemolytica and Pasteurella multocida.

Pradofloxacin-a dual-targeting fluoroquinolone-is the most recent approved for use in food animals. Minimum inhibitory and mutant prevention concentration values were determined for pradofloxacin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin, and tulathromycin. For M. haemolytica strains, MIC50/90/100 values were ≤0.016/≤0.016/≤0.016 and MPC50/90/100 values were 0.031/0.063/0.063; for P. multocida strains, the MIC50/90/100 values ≤0.016/≤0.016/0.031 and MPC50/90/100 ≤ 0.016/0.031/0.063 for pradofloxacin. The pradofloxacin Cmax/MIC90 and Cmax/MPC90 values for M. haemolytica and P. multocida strains, respectively, were 212.5 and 53.9 and 212.5 and 109.7. Similarly, AUC24/MIC90 and AUC24/MPC90 for M. haemolytica were 825 and 209.5, and for P. multocida, they were 825 and 425.8. Pradofloxacin would exceed the mutant selection window for >12-16 h. Pradofloxacin appears to have a low likelihood for resistance selection against key bovine respiratory disease bacterial pathogens based on low MIC and MPC values.

Integrative and conjugative elements of Pasteurella multocida: Prevalence and signatures in population evolution.

Pasteurella multocida (P. multocida) is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in P. multocida and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced P. multocida genomes obtained by high-throughput sequencing together with 393 publicly available P. multocida genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in P. multocida, including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICEHin1056 family, with the latter being widely prevalent in P. multocida and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene blaOXA-2 and the bleomycin gene bleO to P. multocida. Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in P. multocida were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in P. multocida and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.

Dissecting aortitis in a goat associated with Pasteurella multocida and Staphylococcus spp infection.

Reports of primary cardiovascular disease in goats are rare and most commonly include ventricular septal defect, valvular endocarditis, traumatic pericarditis, ionophore poisoning and nutritional cardiomyopathies. We now report the pathological findings in a 67 kg, 6-year-old, adult female Boer goat that presented with neurological signs (ie, head pressing, unsteadiness and paddling) and hyperthermia 2 days prior to death. Lack of therapeutic response to meloxicam and penicillin‒streptomycin and poor prognosis led to euthanasia of the animal. At necropsy, the main findings included severe aortic dissection with luminal thrombosis and stenosis, and pulmonary congestion and oedema. Histological examination of the aorta revealed severe chronic granulomatous and fibrosing dissecting aortitis with mineralization. Bacterial culture of the affected aortic segment resulted in isolation of a profuse growth of Pasteurella multocida and a moderate growth of Staphylococcus spp. Histopathological findings in the central nervous system were consistent with neurolisteriosis.

CXCL8 Knockout: A Key to Resisting Pasteurella multocida Toxin-Induced Cytotoxicity.

Pasteurella multocida, a zoonotic pathogen that produces a 146-kDa modular toxin (PMT), causes progressive atrophic rhinitis with severe turbinate bone degradation in pigs. However, its mechanism of cytotoxicity remains unclear. In this study, we expressed PMT, purified it in a prokaryotic expression system, and found that it killed PK15 cells. The host factor CXCL8 was significantly upregulated among the differentially expressed genes in a transcriptome sequencing analysis and qPCR verification. We constructed a CXCL8-knockout cell line with a CRISPR/Cas9 system and found that CXCL8 knockout significantly increased resistance to PMT-induced cell apoptosis. CXCL8 knockout impaired the cleavage efficiency of apoptosis-related proteins, including Caspase3, Caspase8, and PARP1, as demonstrated with Western blot. In conclusion, these findings establish that CXCL8 facilitates PMT-induced PK15 cell death, which involves apoptotic pathways; this observation documents that CXCL8 plays a key role in PMT-induced PK15 cell death.

Pasteurella multocida From a Cat Scratch as a Cause of Recurrent Prosthetic Joint Infection After Previously Successful Single-Stage Exchange Arthroplasty.

We report a case of a 74-year-old female with a history of a prosthetic joint infection that was successfully treated with a single-stage exchange arthroplasty, off antibiotics, and without symptoms for 20 months. She presented 1 week after a cat scratch with acute knee pain, and aspiration grew Pasteurella multocida. She was successfully treated with surgical debridement and a prolonged course of antibiotics. Debate remains in the literature regarding whether recurrent infections represent a previously undetected organism or a new infection. Our report provides convincing evidence that, at least in some circumstances, the infection is new. Furthermore, this is the first case described of P. multocida resulting in a recurrent prosthetic joint infection after a previously successful exchange arthroplasty due to a different causative organism.

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm.

Pasteurella multocida is an important zoonotic respiratory pathogen capable of infecting a diverse range of hosts, including humans, farm animals, and wild animals. However, the precise mechanisms by which P. multocida compromises the pulmonary integrity of mammals and subsequently induces systemic infection remain largely unexplored. In this study, based on mouse and rabbit models, we found that P. multocida causes not only lung damage but also bacteremia due to the loss of lung integrity. Furthermore, we demonstrated that bacteremia is an important aspect of P. multocida pathogenesis, as evidenced by the observed multiorgan damage and systemic inflammation, and ultimately found that this systemic infection leads to a cytokine storm that can be mitigated by IL-6-neutralizing antibodies. As a result, we divided the pathogenesis of P. multocida into two phases: the pulmonary infection phase and the systemic infection phase. Based on unbiased RNA-seq data, we discovered that P. multocida-induced apoptosis leads to the loss of pulmonary epithelial integrity. These findings have been validated in both TC-1 murine lung epithelial cells and the lungs of model mice. Conversely, the administration of Ac-DEVD-CHO, an apoptosis inhibitor, effectively restored pulmonary epithelial integrity, significantly mitigated lung damage, inhibited bacteremia, attenuated the cytokine storm, and reduced mortality in mouse models. At the molecular level, we demonstrated that the FAK-AKT-FOXO1 axis is involved in P. multocida-induced lung epithelial cell apoptosis in both cells and animals. Thus, our research provides crucial information with regard to the pathogenesis of P. multocida as well as potential treatment options for this and other respiratory bacterial diseases.